Schwirtlich, Marija

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orcid::0000-0002-2183-0164
  • Schwirtlich, Marija (26)
  • Švirtlih, Marija (1)
Projects

Author's Bibliography

The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro

Bojić, Luka; Schwirtlich, Marija; Lazić, Stefan; Stanisavljević Ninković, Danijela; Balint, Vanda; Stevanović, Milena; Milivojević, Milena

(Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, 2023)

TY  - CONF
AU  - Bojić, Luka
AU  - Schwirtlich, Marija
AU  - Lazić, Stefan
AU  - Stanisavljević Ninković, Danijela
AU  - Balint, Vanda
AU  - Stevanović, Milena
AU  - Milivojević, Milena
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2133
AB  - Introduction: Prolonged exposure to sunlight, has a harmful effect on skin cells encompassing reduced
viability, morphological changes, and altered gene expression. The two most prevalent types ofskin cancer,squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), arise from malignant transformation
of keratinocytes. UV radiation, among other factors, serves as the primary cause of these tumors. Previous data hasshown that changesin different SOX genes expression in these cancer types correlates with
disease progression, suggesting their role as oncogenes/tumor suppressors. The presented work is focused on examining the impact of UVB radiation on the expression of SOX2 and SOX9 genesin HaCaT cells
derived from human keratinocytes.
Methods: Using a custom-made UV solarsimulator for the irradiation of HaCaT cells with 150 mJ/cm2 or
300 mJ/cm2
, we analyzed SOX2 and SOX9 gene expression. In order to determine the protective effects
of quercetin, anti-inflammatory bioflavonoid, we treated irradiated HaCaT with quercetin, and analyzed
SOX gene expression.
Results: Our resultsindicate that UVB radiation induces a dose dependent decrease of SOX2 expression
while expression of SOX9 was increased at the dose of 150 mJ/cm2 in HaCaT. Treatment of cells with
quercetin increased the expression of both SOX2 and SOX9 genesin HaCaT cellsfollowing UVB radiation
at both doses compared to irradiated cells.
Conclusions: Further research is needed to understand the molecular mechanisms and significance of
SOX2 and SOX9 in UVB-induced cellular responses, in the context of nonmelanoma cancers with potential implications for targeted therapeutic strategies for nonmelanoma cancers
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro
EP  - 143
SP  - 143
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2133
ER  - 
@conference{
author = "Bojić, Luka and Schwirtlich, Marija and Lazić, Stefan and Stanisavljević Ninković, Danijela and Balint, Vanda and Stevanović, Milena and Milivojević, Milena",
year = "2023",
abstract = "Introduction: Prolonged exposure to sunlight, has a harmful effect on skin cells encompassing reduced
viability, morphological changes, and altered gene expression. The two most prevalent types ofskin cancer,squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), arise from malignant transformation
of keratinocytes. UV radiation, among other factors, serves as the primary cause of these tumors. Previous data hasshown that changesin different SOX genes expression in these cancer types correlates with
disease progression, suggesting their role as oncogenes/tumor suppressors. The presented work is focused on examining the impact of UVB radiation on the expression of SOX2 and SOX9 genesin HaCaT cells
derived from human keratinocytes.
Methods: Using a custom-made UV solarsimulator for the irradiation of HaCaT cells with 150 mJ/cm2 or
300 mJ/cm2
, we analyzed SOX2 and SOX9 gene expression. In order to determine the protective effects
of quercetin, anti-inflammatory bioflavonoid, we treated irradiated HaCaT with quercetin, and analyzed
SOX gene expression.
Results: Our resultsindicate that UVB radiation induces a dose dependent decrease of SOX2 expression
while expression of SOX9 was increased at the dose of 150 mJ/cm2 in HaCaT. Treatment of cells with
quercetin increased the expression of both SOX2 and SOX9 genesin HaCaT cellsfollowing UVB radiation
at both doses compared to irradiated cells.
Conclusions: Further research is needed to understand the molecular mechanisms and significance of
SOX2 and SOX9 in UVB-induced cellular responses, in the context of nonmelanoma cancers with potential implications for targeted therapeutic strategies for nonmelanoma cancers",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro",
pages = "143-143",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2133"
}
Bojić, L., Schwirtlich, M., Lazić, S., Stanisavljević Ninković, D., Balint, V., Stevanović, M.,& Milivojević, M.. (2023). The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 143-143.
https://hdl.handle.net/21.15107/rcub_imagine_2133
Bojić L, Schwirtlich M, Lazić S, Stanisavljević Ninković D, Balint V, Stevanović M, Milivojević M. The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:143-143.
https://hdl.handle.net/21.15107/rcub_imagine_2133 .
Bojić, Luka, Schwirtlich, Marija, Lazić, Stefan, Stanisavljević Ninković, Danijela, Balint, Vanda, Stevanović, Milena, Milivojević, Milena, "The effect of UVB radiation onthe expression of SOX2 and SOX9 genes in human keratinocytes in vitro" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):143-143,
https://hdl.handle.net/21.15107/rcub_imagine_2133 .

SOX transcription factors – choosing between stemness and neuronal differentiation

Švirtlih, Marija

(Belgrade : Serbian Neuroscience Society, 2023)

TY  - CONF
AU  - Švirtlih, Marija
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2183
AB  - The SOX genes show properties of both classical transcription factors and
architectural components of chromatin. As a main part of regulatory networks that
consist of transcription factors, epigenetic modifiers and microRNAs, they govern
diverse cellular processes during embryonic and adult neurogenesis, such as
maintaining the multipotency of neural stem cells, cell fate decision and terminal cell
differentiation.
The sequential expression of the SoxB, SoxC, SoxD, SoxE and/or SoxF group
members in differentiating and mature neurons, oligodendrocytes and astrocytes is
essential for their identity and survival. Several studies revealed that deregulated
expression of these proteins had significant impact on the neuronal plasticity. Results
of our research using both in vivo and in vitro model systems to study neurogenesis in
different brain pathologies, demonstrated decreased expression of SOXB transcription
factor in neural stem/progenitor cells in early stages of neurodegeneration or
following ischemia- related injury that has significant impact on regeneration
capacity. Recently, it has been demonstrated that neural stem cells from SVZ are cells
of origin of glioblastoma, the most common and devastated brain tumor. Our
investigation of SOXB showed deregulated expression of SOX3 protein also in
glioblastoma samples, compared to the expression in non-tumoral brain tissues while
exogenous overexpression of this gene promoted the malignant properties of
glioblastoma cells.
Despite numerous data implicating the key role of Sox/SOX genes in regulation
of neurogenesis, contribution of SOX genes in various brain pathologies is still not
clear. Future studies are needed to evaluate them as a potential targets in therapeutic
and regenerative strategies.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of the Serbian Neuroscience Society
T1  - SOX transcription factors – choosing between stemness and neuronal differentiation
EP  - 35
SP  - 35
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2183
ER  - 
@conference{
author = "Švirtlih, Marija",
year = "2023",
abstract = "The SOX genes show properties of both classical transcription factors and
architectural components of chromatin. As a main part of regulatory networks that
consist of transcription factors, epigenetic modifiers and microRNAs, they govern
diverse cellular processes during embryonic and adult neurogenesis, such as
maintaining the multipotency of neural stem cells, cell fate decision and terminal cell
differentiation.
The sequential expression of the SoxB, SoxC, SoxD, SoxE and/or SoxF group
members in differentiating and mature neurons, oligodendrocytes and astrocytes is
essential for their identity and survival. Several studies revealed that deregulated
expression of these proteins had significant impact on the neuronal plasticity. Results
of our research using both in vivo and in vitro model systems to study neurogenesis in
different brain pathologies, demonstrated decreased expression of SOXB transcription
factor in neural stem/progenitor cells in early stages of neurodegeneration or
following ischemia- related injury that has significant impact on regeneration
capacity. Recently, it has been demonstrated that neural stem cells from SVZ are cells
of origin of glioblastoma, the most common and devastated brain tumor. Our
investigation of SOXB showed deregulated expression of SOX3 protein also in
glioblastoma samples, compared to the expression in non-tumoral brain tissues while
exogenous overexpression of this gene promoted the malignant properties of
glioblastoma cells.
Despite numerous data implicating the key role of Sox/SOX genes in regulation
of neurogenesis, contribution of SOX genes in various brain pathologies is still not
clear. Future studies are needed to evaluate them as a potential targets in therapeutic
and regenerative strategies.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of the Serbian Neuroscience Society",
title = "SOX transcription factors – choosing between stemness and neuronal differentiation",
pages = "35-35",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2183"
}
Švirtlih, M.. (2023). SOX transcription factors – choosing between stemness and neuronal differentiation. in 8th Congress of the Serbian Neuroscience Society
Belgrade : Serbian Neuroscience Society., 35-35.
https://hdl.handle.net/21.15107/rcub_imagine_2183
Švirtlih M. SOX transcription factors – choosing between stemness and neuronal differentiation. in 8th Congress of the Serbian Neuroscience Society. 2023;:35-35.
https://hdl.handle.net/21.15107/rcub_imagine_2183 .
Švirtlih, Marija, "SOX transcription factors – choosing between stemness and neuronal differentiation" in 8th Congress of the Serbian Neuroscience Society (2023):35-35,
https://hdl.handle.net/21.15107/rcub_imagine_2183 .

The Role of SOX Transcription Factors in Ageing and Age-Related Diseases

Stevanović, Milena; Lazić, Andrijana; Schwirtlich, Marija; Stanisavljević Ninković, Danijela

(2023)

TY  - JOUR
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
AU  - Schwirtlich, Marija
AU  - Stanisavljević Ninković, Danijela
PY  - 2023
UR  - https://www.mdpi.com/1422-0067/24/1/851
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1891
AB  - The quest for eternal youth and immortality is as old as humankind. Ageing is an inevitable physiological process accompanied by many functional declines that are driving factors for age-related diseases. Stem cell exhaustion is one of the major hallmarks of ageing. The SOX transcription factors play well-known roles in self-renewal and differentiation of both embryonic and adult stem cells. As a consequence of ageing, the repertoire of adult stem cells present in various organs steadily declines, and their dysfunction/death could lead to reduced regenerative potential and development of age-related diseases. Thus, restoring the function of aged stem cells, inducing their regenerative potential, and slowing down the ageing process are critical for improving the health span and, consequently, the lifespan of humans. Reprograming factors, including SOX family members, emerge as crucial players in rejuvenation. This review focuses on the roles of SOX transcription factors in stem cell exhaustion and age-related diseases, including neurodegenerative diseases, visual deterioration, chronic obstructive pulmonary disease, osteoporosis, and age-related cancers. A better understanding of the molecular mechanisms of ageing and the roles of SOX transcription factors in this process could open new avenues for developing novel strategies that will delay ageing and prevent age-related diseases.
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - The Role of SOX Transcription Factors in Ageing and Age-Related Diseases
IS  - 1
SP  - 851
VL  - 24
DO  - 10.3390/ijms24010851
ER  - 
@article{
author = "Stevanović, Milena and Lazić, Andrijana and Schwirtlich, Marija and Stanisavljević Ninković, Danijela",
year = "2023",
abstract = "The quest for eternal youth and immortality is as old as humankind. Ageing is an inevitable physiological process accompanied by many functional declines that are driving factors for age-related diseases. Stem cell exhaustion is one of the major hallmarks of ageing. The SOX transcription factors play well-known roles in self-renewal and differentiation of both embryonic and adult stem cells. As a consequence of ageing, the repertoire of adult stem cells present in various organs steadily declines, and their dysfunction/death could lead to reduced regenerative potential and development of age-related diseases. Thus, restoring the function of aged stem cells, inducing their regenerative potential, and slowing down the ageing process are critical for improving the health span and, consequently, the lifespan of humans. Reprograming factors, including SOX family members, emerge as crucial players in rejuvenation. This review focuses on the roles of SOX transcription factors in stem cell exhaustion and age-related diseases, including neurodegenerative diseases, visual deterioration, chronic obstructive pulmonary disease, osteoporosis, and age-related cancers. A better understanding of the molecular mechanisms of ageing and the roles of SOX transcription factors in this process could open new avenues for developing novel strategies that will delay ageing and prevent age-related diseases.",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "The Role of SOX Transcription Factors in Ageing and Age-Related Diseases",
number = "1",
pages = "851",
volume = "24",
doi = "10.3390/ijms24010851"
}
Stevanović, M., Lazić, A., Schwirtlich, M.,& Stanisavljević Ninković, D.. (2023). The Role of SOX Transcription Factors in Ageing and Age-Related Diseases. in International Journal of Molecular Sciences, 24(1), 851.
https://doi.org/10.3390/ijms24010851
Stevanović M, Lazić A, Schwirtlich M, Stanisavljević Ninković D. The Role of SOX Transcription Factors in Ageing and Age-Related Diseases. in International Journal of Molecular Sciences. 2023;24(1):851.
doi:10.3390/ijms24010851 .
Stevanović, Milena, Lazić, Andrijana, Schwirtlich, Marija, Stanisavljević Ninković, Danijela, "The Role of SOX Transcription Factors in Ageing and Age-Related Diseases" in International Journal of Molecular Sciences, 24, no. 1 (2023):851,
https://doi.org/10.3390/ijms24010851 . .
5
3
2

Interplay of SOX transcription factors and microRNAs in the brain under physiological and pathological conditions

Stevanović, Milena; Stanisavljević Ninković, Danijela; Mojsin, Marija; Drakulić, Danijela; Schwirtlich, Marija

(Wolters Kluwer Medknow Publications, Mumbai, 2022)

TY  - JOUR
AU  - Stevanović, Milena
AU  - Stanisavljević Ninković, Danijela
AU  - Mojsin, Marija
AU  - Drakulić, Danijela
AU  - Schwirtlich, Marija
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1548
AB  - Precise tuning of gene expression, accomplished by regulatory networks of transcription factors, epigenetic modifiers, and microRNAs, is crucial for the proper neural development and function of the brain cells. The SOX transcription factors are involved in regulating diverse cellular processes during embryonic and adult neurogenesis, such as maintaining the cell stemness, cell proliferation, cell fate decisions, and terminal differentiation into neurons and glial cells. MicroRNAs represent a class of small non-coding RNAs that play important roles in the regulation of gene expression. Together with other gene regulatory factors, microRNAs regulate different processes during neurogenesis and orchestrate the spatial and temporal expression important for neurodevelopment. The emerging data point to a complex regulatory network between SOX transcription factors and microRNAs that govern distinct cellular activities in the developing and adult brain. Deregulated SOX/microRNA interplay in signaling pathways that influence the homeostasis and plasticity in the brain has been revealed in various brain pathologies, including neurodegenerative disorders, traumatic brain injury, and cancer. Therapeutic strategies that target SOX/microRNA interplay have emerged in recent years as a promising tool to target neural tissue regeneration and enhance neurorestoration. Numerous studies have confirmed complex interactions between microRNAs and SOX-specific mRNAs regulating key features of glioblastoma. Keeping in mind the crucial roles of SOX genes and microRNAs in neural development, we focus this review on SOX/microRNAs interplay in the brain during development and adulthood in physiological and pathological conditions. Special focus was made on their interplay in brain pathologies to summarize current knowledge and highlight potential future development of molecular therapies.
PB  - Wolters Kluwer Medknow Publications, Mumbai
T2  - Neural Regeneration Research
T1  - Interplay of SOX transcription factors and microRNAs in the brain under physiological and pathological conditions
EP  - 2334
IS  - 11
SP  - 2325
VL  - 17
DO  - 10.4103/1673-5374.338990
ER  - 
@article{
author = "Stevanović, Milena and Stanisavljević Ninković, Danijela and Mojsin, Marija and Drakulić, Danijela and Schwirtlich, Marija",
year = "2022",
abstract = "Precise tuning of gene expression, accomplished by regulatory networks of transcription factors, epigenetic modifiers, and microRNAs, is crucial for the proper neural development and function of the brain cells. The SOX transcription factors are involved in regulating diverse cellular processes during embryonic and adult neurogenesis, such as maintaining the cell stemness, cell proliferation, cell fate decisions, and terminal differentiation into neurons and glial cells. MicroRNAs represent a class of small non-coding RNAs that play important roles in the regulation of gene expression. Together with other gene regulatory factors, microRNAs regulate different processes during neurogenesis and orchestrate the spatial and temporal expression important for neurodevelopment. The emerging data point to a complex regulatory network between SOX transcription factors and microRNAs that govern distinct cellular activities in the developing and adult brain. Deregulated SOX/microRNA interplay in signaling pathways that influence the homeostasis and plasticity in the brain has been revealed in various brain pathologies, including neurodegenerative disorders, traumatic brain injury, and cancer. Therapeutic strategies that target SOX/microRNA interplay have emerged in recent years as a promising tool to target neural tissue regeneration and enhance neurorestoration. Numerous studies have confirmed complex interactions between microRNAs and SOX-specific mRNAs regulating key features of glioblastoma. Keeping in mind the crucial roles of SOX genes and microRNAs in neural development, we focus this review on SOX/microRNAs interplay in the brain during development and adulthood in physiological and pathological conditions. Special focus was made on their interplay in brain pathologies to summarize current knowledge and highlight potential future development of molecular therapies.",
publisher = "Wolters Kluwer Medknow Publications, Mumbai",
journal = "Neural Regeneration Research",
title = "Interplay of SOX transcription factors and microRNAs in the brain under physiological and pathological conditions",
pages = "2334-2325",
number = "11",
volume = "17",
doi = "10.4103/1673-5374.338990"
}
Stevanović, M., Stanisavljević Ninković, D., Mojsin, M., Drakulić, D.,& Schwirtlich, M.. (2022). Interplay of SOX transcription factors and microRNAs in the brain under physiological and pathological conditions. in Neural Regeneration Research
Wolters Kluwer Medknow Publications, Mumbai., 17(11), 2325-2334.
https://doi.org/10.4103/1673-5374.338990
Stevanović M, Stanisavljević Ninković D, Mojsin M, Drakulić D, Schwirtlich M. Interplay of SOX transcription factors and microRNAs in the brain under physiological and pathological conditions. in Neural Regeneration Research. 2022;17(11):2325-2334.
doi:10.4103/1673-5374.338990 .
Stevanović, Milena, Stanisavljević Ninković, Danijela, Mojsin, Marija, Drakulić, Danijela, Schwirtlich, Marija, "Interplay of SOX transcription factors and microRNAs in the brain under physiological and pathological conditions" in Neural Regeneration Research, 17, no. 11 (2022):2325-2334,
https://doi.org/10.4103/1673-5374.338990 . .
1
7
5

Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma

Drakulić, Danijela; Schwirtlich, Marija; Petrović, Isidora; Mojsin, Marija; Milivojević, Milena; Kovačević Grujičić, Nataša; Stevanović, Milena

(MDPI, Basel, 2022)

TY  - JOUR
AU  - Drakulić, Danijela
AU  - Schwirtlich, Marija
AU  - Petrović, Isidora
AU  - Mojsin, Marija
AU  - Milivojević, Milena
AU  - Kovačević Grujičić, Nataša
AU  - Stevanović, Milena
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1519
AB  - Glioblastoma (GBM) is the most common and highly lethal type of brain tumor, with poor survival despite advances in understanding its complexity. After current standard therapeutic treatment, including tumor resection, radiotherapy and concomitant chemotherapy with temozolomide, the median overall survival of patients with this type of tumor is less than 15 months. Thus, there is an urgent need for new insights into GBM molecular characteristics and progress in targeted therapy in order to improve clinical outcomes. The literature data revealed that a number of different signaling pathways are dysregulated in GBM. In this review, we intended to summarize and discuss current literature data and therapeutic modalities focused on targeting dysregulated signaling pathways in GBM. A better understanding of opportunities for targeting signaling pathways that influences malignant behavior of GBM cells might open the way for the development of novel GBM-targeted therapies.
PB  - MDPI, Basel
T2  - Cells
T1  - Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma
IS  - 16
VL  - 11
DO  - 10.3390/cells11162530
ER  - 
@article{
author = "Drakulić, Danijela and Schwirtlich, Marija and Petrović, Isidora and Mojsin, Marija and Milivojević, Milena and Kovačević Grujičić, Nataša and Stevanović, Milena",
year = "2022",
abstract = "Glioblastoma (GBM) is the most common and highly lethal type of brain tumor, with poor survival despite advances in understanding its complexity. After current standard therapeutic treatment, including tumor resection, radiotherapy and concomitant chemotherapy with temozolomide, the median overall survival of patients with this type of tumor is less than 15 months. Thus, there is an urgent need for new insights into GBM molecular characteristics and progress in targeted therapy in order to improve clinical outcomes. The literature data revealed that a number of different signaling pathways are dysregulated in GBM. In this review, we intended to summarize and discuss current literature data and therapeutic modalities focused on targeting dysregulated signaling pathways in GBM. A better understanding of opportunities for targeting signaling pathways that influences malignant behavior of GBM cells might open the way for the development of novel GBM-targeted therapies.",
publisher = "MDPI, Basel",
journal = "Cells",
title = "Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma",
number = "16",
volume = "11",
doi = "10.3390/cells11162530"
}
Drakulić, D., Schwirtlich, M., Petrović, I., Mojsin, M., Milivojević, M., Kovačević Grujičić, N.,& Stevanović, M.. (2022). Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma. in Cells
MDPI, Basel., 11(16).
https://doi.org/10.3390/cells11162530
Drakulić D, Schwirtlich M, Petrović I, Mojsin M, Milivojević M, Kovačević Grujičić N, Stevanović M. Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma. in Cells. 2022;11(16).
doi:10.3390/cells11162530 .
Drakulić, Danijela, Schwirtlich, Marija, Petrović, Isidora, Mojsin, Marija, Milivojević, Milena, Kovačević Grujičić, Nataša, Stevanović, Milena, "Current Opportunities for Targeting Dysregulated Neurodevelopmental Signaling Pathways in Glioblastoma" in Cells, 11, no. 16 (2022),
https://doi.org/10.3390/cells11162530 . .
1
12
9

Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells

Lazić, Stefan; Dužanić, Filip; Stanisavljević Ninković, Danijela; Drakulić, Danijela; Mojsin, Marija; Milojević, Milena; Balinat, Vanda; Petrović, Isidora; Kovačević Grujičić, Nataša ; Schwirtlich, Marija; Stevanović, Milena

(2022)

TY  - CONF
AU  - Lazić, Stefan
AU  - Dužanić, Filip
AU  - Stanisavljević Ninković, Danijela
AU  - Drakulić, Danijela
AU  - Mojsin, Marija
AU  - Milojević, Milena
AU  - Balinat, Vanda
AU  - Petrović, Isidora
AU  - Kovačević Grujičić, Nataša 
AU  - Schwirtlich, Marija
AU  - Stevanović, Milena
PY  - 2022
UR  - https://doi.org/10.21175/rad.spr.abstr.book.2022.22.2
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1865
AB  - The family of SOX genes encodes proteins that display properties of both classical transcription factors and architectural components of chromatin. During development of nervous system, as well as adult neurogenesis, SOX transcription factors govern diverse cellular processes such as maintaining the multipotency of neural stem cells, cell proliferation, cell fate decision, migration as well as terminal differentiation of neurons. Despite their well-known function in development and brain homeostasis, the expression and role of these genes in pathology- induced neural stem cell plasticity is poorly understood. Reduction in oxygen supply or ischemia are involved in various pathological conditions, such as stroke, traumatic brain injury and cardiac arrest, which promotes neurogenesis, angiogenesis, cell proliferation and other cell mechanisms for survival under the stress. The aim of the present study was to analyze the expression of SOX genes during in vitro neurogenesis following chemical hypoxia. Neuronal differentiation of human pluripotent embryonal carcinoma stem cell line NT2/D1 was used as an in vitro model system for studying the process of human neurogenesis. Depending on different concentration, RA directed the differentiation of NT2/D1 cells into neurons with a different phenotype. The effect of stress caused by hypoxia on the properties of pluripotent cells as well as the induction of neural differentiation was monitored in vitro by culturing NT2/D1 cells in the presence of cobalt chloride, a chemical inducer of hypoxia. The results of the analysis showed that the effect of hypoxia on the expression of SOX2 and OCT4 proteins involved in maintaining the pluripotency of cells depends on the duration of action of cobalt chloride. After short-term exposure of the cells, an increase in the levels of expression of SOX2 and OCT4 proteins was detected, while long-term treatment of the cells led to a decrease in the expression of these proteins. Furthermore, results showed that depending of duration of cobalt chloride treatments, the level of expression of miR-21 in undifferentiated NT2/D1 cells significantly changed. In addition, long-term pretreatment of pluripotent cells with cobalt chloride resulted in increased expression levels of SOX2, SOX3 and GAD67 proteins in neural progenitors induced for 7 days in the presence of, either low or high concentration of retinoic acid, indicating that hypoxia causes increased efficiency of NT2/D1 cell neural differentiation. Damage of brain tissue caused by reduction of oxygen and/or blood flow to the tissue is the leading cause of death worldwide and the leading cause of disability in humans. Our results contributes to the research focused on discovering the roles of SOX TFs and their gene targets in ischemia related pathologies, making them promising biomarkers and potential targets for future diagnostic and therapeutic strategies.
C3  - RAD International concerence on radiation in various fields of research
T1  - Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells
IS  - Spring Edition
SP  - 91
DO  - 10.21175/rad.spr.abstr.book.2022.22.2
ER  - 
@conference{
author = "Lazić, Stefan and Dužanić, Filip and Stanisavljević Ninković, Danijela and Drakulić, Danijela and Mojsin, Marija and Milojević, Milena and Balinat, Vanda and Petrović, Isidora and Kovačević Grujičić, Nataša  and Schwirtlich, Marija and Stevanović, Milena",
year = "2022",
abstract = "The family of SOX genes encodes proteins that display properties of both classical transcription factors and architectural components of chromatin. During development of nervous system, as well as adult neurogenesis, SOX transcription factors govern diverse cellular processes such as maintaining the multipotency of neural stem cells, cell proliferation, cell fate decision, migration as well as terminal differentiation of neurons. Despite their well-known function in development and brain homeostasis, the expression and role of these genes in pathology- induced neural stem cell plasticity is poorly understood. Reduction in oxygen supply or ischemia are involved in various pathological conditions, such as stroke, traumatic brain injury and cardiac arrest, which promotes neurogenesis, angiogenesis, cell proliferation and other cell mechanisms for survival under the stress. The aim of the present study was to analyze the expression of SOX genes during in vitro neurogenesis following chemical hypoxia. Neuronal differentiation of human pluripotent embryonal carcinoma stem cell line NT2/D1 was used as an in vitro model system for studying the process of human neurogenesis. Depending on different concentration, RA directed the differentiation of NT2/D1 cells into neurons with a different phenotype. The effect of stress caused by hypoxia on the properties of pluripotent cells as well as the induction of neural differentiation was monitored in vitro by culturing NT2/D1 cells in the presence of cobalt chloride, a chemical inducer of hypoxia. The results of the analysis showed that the effect of hypoxia on the expression of SOX2 and OCT4 proteins involved in maintaining the pluripotency of cells depends on the duration of action of cobalt chloride. After short-term exposure of the cells, an increase in the levels of expression of SOX2 and OCT4 proteins was detected, while long-term treatment of the cells led to a decrease in the expression of these proteins. Furthermore, results showed that depending of duration of cobalt chloride treatments, the level of expression of miR-21 in undifferentiated NT2/D1 cells significantly changed. In addition, long-term pretreatment of pluripotent cells with cobalt chloride resulted in increased expression levels of SOX2, SOX3 and GAD67 proteins in neural progenitors induced for 7 days in the presence of, either low or high concentration of retinoic acid, indicating that hypoxia causes increased efficiency of NT2/D1 cell neural differentiation. Damage of brain tissue caused by reduction of oxygen and/or blood flow to the tissue is the leading cause of death worldwide and the leading cause of disability in humans. Our results contributes to the research focused on discovering the roles of SOX TFs and their gene targets in ischemia related pathologies, making them promising biomarkers and potential targets for future diagnostic and therapeutic strategies.",
journal = "RAD International concerence on radiation in various fields of research",
title = "Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells",
number = "Spring Edition",
pages = "91",
doi = "10.21175/rad.spr.abstr.book.2022.22.2"
}
Lazić, S., Dužanić, F., Stanisavljević Ninković, D., Drakulić, D., Mojsin, M., Milojević, M., Balinat, V., Petrović, I., Kovačević Grujičić, N., Schwirtlich, M.,& Stevanović, M.. (2022). Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells. in RAD International concerence on radiation in various fields of research(Spring Edition), 91.
https://doi.org/10.21175/rad.spr.abstr.book.2022.22.2
Lazić S, Dužanić F, Stanisavljević Ninković D, Drakulić D, Mojsin M, Milojević M, Balinat V, Petrović I, Kovačević Grujičić N, Schwirtlich M, Stevanović M. Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells. in RAD International concerence on radiation in various fields of research. 2022;(Spring Edition):91.
doi:10.21175/rad.spr.abstr.book.2022.22.2 .
Lazić, Stefan, Dužanić, Filip, Stanisavljević Ninković, Danijela, Drakulić, Danijela, Mojsin, Marija, Milojević, Milena, Balinat, Vanda, Petrović, Isidora, Kovačević Grujičić, Nataša , Schwirtlich, Marija, Stevanović, Milena, "Hypoxia affects the expression of SOX genes and induction of neural differentiation of human embryonal carcinoma NT2/D1 cells" in RAD International concerence on radiation in various fields of research, no. Spring Edition (2022):91,
https://doi.org/10.21175/rad.spr.abstr.book.2022.22.2 . .

Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells

Petrović, Isidora; Milivojević, Milena; Arsenijević, Ana; Lazić, Andrijana; Kovačević Grujičić, Nataša; Schwirtlich, Marija; Popović, Jelena; Stevanović, Milena

(Tech Science Press, Henderson, 2021)

TY  - JOUR
AU  - Petrović, Isidora
AU  - Milivojević, Milena
AU  - Arsenijević, Ana
AU  - Lazić, Andrijana
AU  - Kovačević Grujičić, Nataša
AU  - Schwirtlich, Marija
AU  - Popović, Jelena
AU  - Stevanović, Milena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1505
AB  - Genetic and molecular heterogeneity, together with intrinsic and acquired resistance to therapy, represent the major obstacles to the successful treatment of different types of breast carcinoma. Increasing evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade, poor prognosis, and therapy resistance. Both SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas, and these genes are recognized as potential antitumor targets. Our aim was to evaluate the effect of retinoic acid (RA), a well-known cyto-differentiating agent, on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 genes. By applying various experimental approaches, we evaluated the effect of RA on basic cellular processes in SK-BR-3 and MCF7 breast carcinoma cell lines. We have shown that RA inhibits cell growth, reduces the number of Ki-67 positive cells, and causes cell-cycle arrest. RA effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression, including a higher decrease in cell viability, reduction in colony formation, and significant remodeling of cellular structure. We have shown that RA treatment led to the downregulation of SOX2 expression in MCF7 cells and to the reduction of SOX18 expression in both cell lines. By functional analysis, we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2, pointing to a SOX2-independent mechanism of action. The ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from non-responders. Together, our study shows that the response of breast carcinoma cell lines to RA treatment may vary, highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes.
PB  - Tech Science Press, Henderson
T2  - Biocell
T1  - Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells
EP  - 1367
IS  - 5
SP  - 1355
VL  - 45
DO  - 10.32604/biocell.2021.015817
ER  - 
@article{
author = "Petrović, Isidora and Milivojević, Milena and Arsenijević, Ana and Lazić, Andrijana and Kovačević Grujičić, Nataša and Schwirtlich, Marija and Popović, Jelena and Stevanović, Milena",
year = "2021",
abstract = "Genetic and molecular heterogeneity, together with intrinsic and acquired resistance to therapy, represent the major obstacles to the successful treatment of different types of breast carcinoma. Increasing evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade, poor prognosis, and therapy resistance. Both SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas, and these genes are recognized as potential antitumor targets. Our aim was to evaluate the effect of retinoic acid (RA), a well-known cyto-differentiating agent, on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 genes. By applying various experimental approaches, we evaluated the effect of RA on basic cellular processes in SK-BR-3 and MCF7 breast carcinoma cell lines. We have shown that RA inhibits cell growth, reduces the number of Ki-67 positive cells, and causes cell-cycle arrest. RA effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression, including a higher decrease in cell viability, reduction in colony formation, and significant remodeling of cellular structure. We have shown that RA treatment led to the downregulation of SOX2 expression in MCF7 cells and to the reduction of SOX18 expression in both cell lines. By functional analysis, we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2, pointing to a SOX2-independent mechanism of action. The ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from non-responders. Together, our study shows that the response of breast carcinoma cell lines to RA treatment may vary, highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes.",
publisher = "Tech Science Press, Henderson",
journal = "Biocell",
title = "Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells",
pages = "1367-1355",
number = "5",
volume = "45",
doi = "10.32604/biocell.2021.015817"
}
Petrović, I., Milivojević, M., Arsenijević, A., Lazić, A., Kovačević Grujičić, N., Schwirtlich, M., Popović, J.,& Stevanović, M.. (2021). Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells. in Biocell
Tech Science Press, Henderson., 45(5), 1355-1367.
https://doi.org/10.32604/biocell.2021.015817
Petrović I, Milivojević M, Arsenijević A, Lazić A, Kovačević Grujičić N, Schwirtlich M, Popović J, Stevanović M. Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells. in Biocell. 2021;45(5):1355-1367.
doi:10.32604/biocell.2021.015817 .
Petrović, Isidora, Milivojević, Milena, Arsenijević, Ana, Lazić, Andrijana, Kovačević Grujičić, Nataša, Schwirtlich, Marija, Popović, Jelena, Stevanović, Milena, "Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells" in Biocell, 45, no. 5 (2021):1355-1367,
https://doi.org/10.32604/biocell.2021.015817 . .
3
3

SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis

Stevanović, Milena; Drakulić, Danijela; Lazić, Andrijana; Stanisavljević Ninković, Danijela; Schwirtlich, Marija; Mojsin, Marija

(Frontiers Media Sa, Lausanne, 2021)

TY  - JOUR
AU  - Stevanović, Milena
AU  - Drakulić, Danijela
AU  - Lazić, Andrijana
AU  - Stanisavljević Ninković, Danijela
AU  - Schwirtlich, Marija
AU  - Mojsin, Marija
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1419
AB  - The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties of both classical TFs and architectural components of chromatin. Since the cloning of the Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players in the regulation of multiple developmental and physiological processes. SOX TFs govern diverse cellular processes during development, such as maintaining the pluripotency of stem cells, cell proliferation, cell fate decisions/germ layer formation as well as terminal cell differentiation into tissues and organs. However, their roles are not limited to development since SOX proteins influence survival, regeneration, cell death and control homeostasis in adult tissues. This review summarized current knowledge of the roles of SOX proteins in control of central nervous system development. Some SOX TFs suspend neural progenitors in proliferative, stem-like state and prevent their differentiation. SOX proteins function as pioneer factors that occupy silenced target genes and keep them in a poised state for activation at subsequent stages of differentiation. At appropriate stage of development, SOX members that maintain stemness are down-regulated in cells that are competent to differentiate, while other SOX members take over their functions and govern the process of differentiation. Distinct SOX members determine down-stream processes of neuronal and glial differentiation. Thus, sequentially acting SOX TFs orchestrate neural lineage development defining neuronal and glial phenotypes. In line with their crucial roles in the nervous system development, deregulation of specific SOX proteins activities is associated with neurodevelopmental disorders (NDDs). The overview of the current knowledge about the link between SOX gene variants and NDDs is presented. We outline the roles of SOX TFs in adult neurogenesis and brain homeostasis and discuss whether impaired adult neurogenesis, detected in neurodegenerative diseases, could be associated with deregulation of SOX proteins activities. We present the current data regarding the interaction between SOX proteins and signaling pathways and microRNAs that play roles in nervous system development. Finally, future research directions that will improve the knowledge about distinct and various roles of SOX TFs in health and diseases are presented and discussed.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Molecular Neuroscience
T1  - SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis
VL  - 14
DO  - 10.3389/fnmol.2021.654031
ER  - 
@article{
author = "Stevanović, Milena and Drakulić, Danijela and Lazić, Andrijana and Stanisavljević Ninković, Danijela and Schwirtlich, Marija and Mojsin, Marija",
year = "2021",
abstract = "The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties of both classical TFs and architectural components of chromatin. Since the cloning of the Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players in the regulation of multiple developmental and physiological processes. SOX TFs govern diverse cellular processes during development, such as maintaining the pluripotency of stem cells, cell proliferation, cell fate decisions/germ layer formation as well as terminal cell differentiation into tissues and organs. However, their roles are not limited to development since SOX proteins influence survival, regeneration, cell death and control homeostasis in adult tissues. This review summarized current knowledge of the roles of SOX proteins in control of central nervous system development. Some SOX TFs suspend neural progenitors in proliferative, stem-like state and prevent their differentiation. SOX proteins function as pioneer factors that occupy silenced target genes and keep them in a poised state for activation at subsequent stages of differentiation. At appropriate stage of development, SOX members that maintain stemness are down-regulated in cells that are competent to differentiate, while other SOX members take over their functions and govern the process of differentiation. Distinct SOX members determine down-stream processes of neuronal and glial differentiation. Thus, sequentially acting SOX TFs orchestrate neural lineage development defining neuronal and glial phenotypes. In line with their crucial roles in the nervous system development, deregulation of specific SOX proteins activities is associated with neurodevelopmental disorders (NDDs). The overview of the current knowledge about the link between SOX gene variants and NDDs is presented. We outline the roles of SOX TFs in adult neurogenesis and brain homeostasis and discuss whether impaired adult neurogenesis, detected in neurodegenerative diseases, could be associated with deregulation of SOX proteins activities. We present the current data regarding the interaction between SOX proteins and signaling pathways and microRNAs that play roles in nervous system development. Finally, future research directions that will improve the knowledge about distinct and various roles of SOX TFs in health and diseases are presented and discussed.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Molecular Neuroscience",
title = "SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis",
volume = "14",
doi = "10.3389/fnmol.2021.654031"
}
Stevanović, M., Drakulić, D., Lazić, A., Stanisavljević Ninković, D., Schwirtlich, M.,& Mojsin, M.. (2021). SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis. in Frontiers in Molecular Neuroscience
Frontiers Media Sa, Lausanne., 14.
https://doi.org/10.3389/fnmol.2021.654031
Stevanović M, Drakulić D, Lazić A, Stanisavljević Ninković D, Schwirtlich M, Mojsin M. SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis. in Frontiers in Molecular Neuroscience. 2021;14.
doi:10.3389/fnmol.2021.654031 .
Stevanović, Milena, Drakulić, Danijela, Lazić, Andrijana, Stanisavljević Ninković, Danijela, Schwirtlich, Marija, Mojsin, Marija, "SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis" in Frontiers in Molecular Neuroscience, 14 (2021),
https://doi.org/10.3389/fnmol.2021.654031 . .
1
76
1
50

Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions

Stojković, Dejan; Drakulić, Danijela; Schwirtlich, Marija; Rajcević, Nemanja; Stevanović, Milena; Soković, Marina D.; Gašić, Uroš

(MDPI, Basel, 2021)

TY  - JOUR
AU  - Stojković, Dejan
AU  - Drakulić, Danijela
AU  - Schwirtlich, Marija
AU  - Rajcević, Nemanja
AU  - Stevanović, Milena
AU  - Soković, Marina D.
AU  - Gašić, Uroš
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1489
AB  - Anthriscus cerefolium (L.) Hoffm. is a plant traditionally used around the globe since antiquity. Although widely used in many traditional medicines in different cultures, from the scientific point of view it is poorly investigated. Glioblastoma, a tumor type with poor prognosis, is the most common and lethal brain tumor in adults. Current therapeutic strategies for glioblastoma include surgery, radiation and chemotherapy. On the other hand, it has been revealed that patients with cancers are highly susceptible to microbial infections due to the invasive nature of cancer treatment approaches. This study was designed to investigate the chemical profile of herba Anthriscii cerefoli methanolic extract by applying UHPLC-LTQ OrbiTrap MS4 analysis and to analyze its anti-glioblastoma and antimicrobial activities. This study revealed that methanolic extract of herba Anthrisc cerefolii contained phenolic acids and flavonoids, with 32 compounds being identified. Anti-glioblastoma activity was investigated in vitro using A172 glioblastoma cell line. The cytotoxic effects of the extract on A172 cells were compared to the same effect on primary human gingival fibroblast (HGF-1) cells. Decreased rate of proliferation and changes in cell morphology were detected upon treatment of A172 cells with the extract. The antimicrobial activity of extract was tested against Staphylococcus aureus and Candida species. The extract was active against the tested bacterium and yeasts, inhibiting free floating cells and microbial biofilms. This study is the first one to provide a detailed description of the chemical profile of A. cerefolium extract dealing with scientific insights into its anti-glioblastoma and antimicrobial activities.
PB  - MDPI, Basel
T2  - Pharmaceuticals
T1  - Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions
IS  - 1
VL  - 14
DO  - 10.3390/ph14010055
ER  - 
@article{
author = "Stojković, Dejan and Drakulić, Danijela and Schwirtlich, Marija and Rajcević, Nemanja and Stevanović, Milena and Soković, Marina D. and Gašić, Uroš",
year = "2021",
abstract = "Anthriscus cerefolium (L.) Hoffm. is a plant traditionally used around the globe since antiquity. Although widely used in many traditional medicines in different cultures, from the scientific point of view it is poorly investigated. Glioblastoma, a tumor type with poor prognosis, is the most common and lethal brain tumor in adults. Current therapeutic strategies for glioblastoma include surgery, radiation and chemotherapy. On the other hand, it has been revealed that patients with cancers are highly susceptible to microbial infections due to the invasive nature of cancer treatment approaches. This study was designed to investigate the chemical profile of herba Anthriscii cerefoli methanolic extract by applying UHPLC-LTQ OrbiTrap MS4 analysis and to analyze its anti-glioblastoma and antimicrobial activities. This study revealed that methanolic extract of herba Anthrisc cerefolii contained phenolic acids and flavonoids, with 32 compounds being identified. Anti-glioblastoma activity was investigated in vitro using A172 glioblastoma cell line. The cytotoxic effects of the extract on A172 cells were compared to the same effect on primary human gingival fibroblast (HGF-1) cells. Decreased rate of proliferation and changes in cell morphology were detected upon treatment of A172 cells with the extract. The antimicrobial activity of extract was tested against Staphylococcus aureus and Candida species. The extract was active against the tested bacterium and yeasts, inhibiting free floating cells and microbial biofilms. This study is the first one to provide a detailed description of the chemical profile of A. cerefolium extract dealing with scientific insights into its anti-glioblastoma and antimicrobial activities.",
publisher = "MDPI, Basel",
journal = "Pharmaceuticals",
title = "Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions",
number = "1",
volume = "14",
doi = "10.3390/ph14010055"
}
Stojković, D., Drakulić, D., Schwirtlich, M., Rajcević, N., Stevanović, M., Soković, M. D.,& Gašić, U.. (2021). Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions. in Pharmaceuticals
MDPI, Basel., 14(1).
https://doi.org/10.3390/ph14010055
Stojković D, Drakulić D, Schwirtlich M, Rajcević N, Stevanović M, Soković MD, Gašić U. Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions. in Pharmaceuticals. 2021;14(1).
doi:10.3390/ph14010055 .
Stojković, Dejan, Drakulić, Danijela, Schwirtlich, Marija, Rajcević, Nemanja, Stevanović, Milena, Soković, Marina D., Gašić, Uroš, "Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions" in Pharmaceuticals, 14, no. 1 (2021),
https://doi.org/10.3390/ph14010055 . .
13
9
3
9

Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats

Todorović, Nevena; Micić, Bojana; Schwirtlich, Marija; Stevanović, Milena; Filipović, Dragana

(Pergamon-Elsevier Science Ltd, Oxford, 2019)

TY  - JOUR
AU  - Todorović, Nevena
AU  - Micić, Bojana
AU  - Schwirtlich, Marija
AU  - Stevanović, Milena
AU  - Filipović, Dragana
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1253
AB  - Dysregulation of GABAergic system is becoming increasingly associated with depression, psychiatric disorder that imposes severe clinical, social and economic burden. Special attention is paid to the fast-spiking parvalbumin-positive (PV+) interneurons, GABAergic neurons which are highly susceptible to redox dysregulation and oxidative stress and implicated in a variety of psychiatric diseases. Here we analyzed the number of PV+ and cleaved caspase-3-positive (CC3+) cells in the rat medial prefrontal cortical (mPFC) subregions following chronic social isolation (CSIS), an animal model of depression and schizophrenia. Also, we examined potential protective effects of antidepressant fluoxetine (FLX) and atypical antipsychotic clozapine (CLZ) on the number of these cells in mPFC subregions, when applied parallel with CSIS in doses that correspond to therapeutically effective ones in patients. Immunofluorescence analysis revealed decreased number of PV+ cells in cingulate cortex area 1, prelimbic area (PrL), infralimbic area (IL) and dorsal peduncular cortex of the mPFC in isolated rats, which coincided with depressive- and anxiety-like behaviors. In addition, CSIS-induced increase in the number of CC3+ cells was detected in aforementioned subregions of mPFC. Treatments with either FLX or CLZ prevented behavioral changes, decrease in PV+ and increase in CC3+ cell numbers in PrL and IL subregions in isolated rats. These results indicate the importance of intact GABAergic signaling in these areas for resistance against CSIS-induced behavioral changes, as well as subregion-specific protective effects of FLX and CLZ in mPFC of CSIS rats.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Neuroscience
T1  - Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats
EP  - 35
SP  - 24
VL  - 396
DO  - 10.1016/j.neuroscience.2018.11.008
ER  - 
@article{
author = "Todorović, Nevena and Micić, Bojana and Schwirtlich, Marija and Stevanović, Milena and Filipović, Dragana",
year = "2019",
abstract = "Dysregulation of GABAergic system is becoming increasingly associated with depression, psychiatric disorder that imposes severe clinical, social and economic burden. Special attention is paid to the fast-spiking parvalbumin-positive (PV+) interneurons, GABAergic neurons which are highly susceptible to redox dysregulation and oxidative stress and implicated in a variety of psychiatric diseases. Here we analyzed the number of PV+ and cleaved caspase-3-positive (CC3+) cells in the rat medial prefrontal cortical (mPFC) subregions following chronic social isolation (CSIS), an animal model of depression and schizophrenia. Also, we examined potential protective effects of antidepressant fluoxetine (FLX) and atypical antipsychotic clozapine (CLZ) on the number of these cells in mPFC subregions, when applied parallel with CSIS in doses that correspond to therapeutically effective ones in patients. Immunofluorescence analysis revealed decreased number of PV+ cells in cingulate cortex area 1, prelimbic area (PrL), infralimbic area (IL) and dorsal peduncular cortex of the mPFC in isolated rats, which coincided with depressive- and anxiety-like behaviors. In addition, CSIS-induced increase in the number of CC3+ cells was detected in aforementioned subregions of mPFC. Treatments with either FLX or CLZ prevented behavioral changes, decrease in PV+ and increase in CC3+ cell numbers in PrL and IL subregions in isolated rats. These results indicate the importance of intact GABAergic signaling in these areas for resistance against CSIS-induced behavioral changes, as well as subregion-specific protective effects of FLX and CLZ in mPFC of CSIS rats.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Neuroscience",
title = "Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats",
pages = "35-24",
volume = "396",
doi = "10.1016/j.neuroscience.2018.11.008"
}
Todorović, N., Micić, B., Schwirtlich, M., Stevanović, M.,& Filipović, D.. (2019). Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats. in Neuroscience
Pergamon-Elsevier Science Ltd, Oxford., 396, 24-35.
https://doi.org/10.1016/j.neuroscience.2018.11.008
Todorović N, Micić B, Schwirtlich M, Stevanović M, Filipović D. Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats. in Neuroscience. 2019;396:24-35.
doi:10.1016/j.neuroscience.2018.11.008 .
Todorović, Nevena, Micić, Bojana, Schwirtlich, Marija, Stevanović, Milena, Filipović, Dragana, "Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats" in Neuroscience, 396 (2019):24-35,
https://doi.org/10.1016/j.neuroscience.2018.11.008 . .
28
14
25

Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors

Zaletel, Ivan; Schwirtlich, Marija; Perović, Milka; Jovanović, Mirna; Stevanović, Milena; Kanazir, Selma; Puskas, Nela

(IOS Press, Amsterdam, 2018)

TY  - JOUR
AU  - Zaletel, Ivan
AU  - Schwirtlich, Marija
AU  - Perović, Milka
AU  - Jovanović, Mirna
AU  - Stevanović, Milena
AU  - Kanazir, Selma
AU  - Puskas, Nela
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1101
AB  - Dysregulation of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus has been related to cognitive deficits and memory loss in neurodegenerative diseases, such as Alzheimer's disease (AD). Members of the B group of SOX transcription factors play critical roles in regulating neurogenesis in the embryonic and adult nervous system, including maintaining the multipotency, renewal, and cell fate decision of neural stem/progenitor cells. The aim of the present study was to evaluate the expression patterns of selected SOXB proteins in the SGZ, of 8-week-old male and female 5xFAD mice, which represent a transgenic model of AD with a severe and very early development of amyloid pathology Immunohistochemical analysis showed a significant decrease in the number of cells expressing SOX1, SOX2, and SOX21 transcription factors within the SGZ of 5xFAD mice in comparison to their non-transgenic counterparts which coincidences with reduced number of doublecortin immunoreactive immature neurons found in Tg males. Despite observed changes in expressional pattern of examined SOXB proteins, the proliferative capacity evaluated by the number of Ki-67 immunoreactive cells remained unaffected in transgenic mice of both genders. Based on our results, we suggest that SOXB proteins might be considered as new biomarkers for the detection of early impairments in adult neurogenesis in different animal models or/and new targets in human regenerative medicine.
PB  - IOS Press, Amsterdam
T2  - Journal of Alzheimers Disease
T1  - Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors
EP  - 976
IS  - 3
SP  - 963
VL  - 65
DO  - 10.3233/JAD-180277
ER  - 
@article{
author = "Zaletel, Ivan and Schwirtlich, Marija and Perović, Milka and Jovanović, Mirna and Stevanović, Milena and Kanazir, Selma and Puskas, Nela",
year = "2018",
abstract = "Dysregulation of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus has been related to cognitive deficits and memory loss in neurodegenerative diseases, such as Alzheimer's disease (AD). Members of the B group of SOX transcription factors play critical roles in regulating neurogenesis in the embryonic and adult nervous system, including maintaining the multipotency, renewal, and cell fate decision of neural stem/progenitor cells. The aim of the present study was to evaluate the expression patterns of selected SOXB proteins in the SGZ, of 8-week-old male and female 5xFAD mice, which represent a transgenic model of AD with a severe and very early development of amyloid pathology Immunohistochemical analysis showed a significant decrease in the number of cells expressing SOX1, SOX2, and SOX21 transcription factors within the SGZ of 5xFAD mice in comparison to their non-transgenic counterparts which coincidences with reduced number of doublecortin immunoreactive immature neurons found in Tg males. Despite observed changes in expressional pattern of examined SOXB proteins, the proliferative capacity evaluated by the number of Ki-67 immunoreactive cells remained unaffected in transgenic mice of both genders. Based on our results, we suggest that SOXB proteins might be considered as new biomarkers for the detection of early impairments in adult neurogenesis in different animal models or/and new targets in human regenerative medicine.",
publisher = "IOS Press, Amsterdam",
journal = "Journal of Alzheimers Disease",
title = "Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors",
pages = "976-963",
number = "3",
volume = "65",
doi = "10.3233/JAD-180277"
}
Zaletel, I., Schwirtlich, M., Perović, M., Jovanović, M., Stevanović, M., Kanazir, S.,& Puskas, N.. (2018). Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors. in Journal of Alzheimers Disease
IOS Press, Amsterdam., 65(3), 963-976.
https://doi.org/10.3233/JAD-180277
Zaletel I, Schwirtlich M, Perović M, Jovanović M, Stevanović M, Kanazir S, Puskas N. Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors. in Journal of Alzheimers Disease. 2018;65(3):963-976.
doi:10.3233/JAD-180277 .
Zaletel, Ivan, Schwirtlich, Marija, Perović, Milka, Jovanović, Mirna, Stevanović, Milena, Kanazir, Selma, Puskas, Nela, "Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors" in Journal of Alzheimers Disease, 65, no. 3 (2018):963-976,
https://doi.org/10.3233/JAD-180277 . .
1
29
10
25

All-trans retinoic acid influences viability, migration and adhesion of U251 glioblastoma cells

Vicentić, Jelena Marjanovic; Schwirtlich, Marija; Kovačević Grujičić, Nataša; Stevanović, Milena; Drakulić, Danijela

(Srpsko biološko društvo, Beograd, i dr., 2017)

TY  - JOUR
AU  - Vicentić, Jelena Marjanovic
AU  - Schwirtlich, Marija
AU  - Kovačević Grujičić, Nataša
AU  - Stevanović, Milena
AU  - Drakulić, Danijela
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1007
AB  - Glioblastoma (GBM) is one of the most aggressive and deadly forms of cancer. Literature data reveals that all-trans retinoic acid (ATRA) has anticancer effects on different types of tumor cells. However, data about the effects of ATRA on glioblastoma cells are contradictory. In this study, we examined whether ATRA treatment affects features of human glioblastoma U251 cells. To that end, the cells were treated with different concentrations of ATRA. Results obtained by MTT and the crystal violet assays imply that ATRA affected the viability of U251 glioblastoma cells in a dose-and time-dependent manner. Fluorescence staining of microtubule cytoskeleton protein a-tubulin revealed that ATRA induced changes in cell morphology. Using semi-quantitative RT-PCR we found that the expression of SOX3 and GFAP genes, as markers of neural differentiation, was not changed upon ATRA treatment. Thus, the observed changes in cell morphology after ATRA treatment are not associated with neural differentiation of U251 glioblastoma cells. The scratch-wound healing assay revealed that ATRA changed the mode of U251 cell migration from collective to single cell motility. The cell-matrix adhesion assay demonstrated that the pharmacologically relevant concentration of ATRA lowered the cell-matrix adhesion capability of U251 cells. In conclusion, our results imply that further studies are needed before ATRA could be considered for the treatment of glioblastoma.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - All-trans retinoic acid influences viability, migration and adhesion of U251 glioblastoma cells
EP  - 706
IS  - 4
SP  - 699
VL  - 69
DO  - 10.2298/ABS170327016M
ER  - 
@article{
author = "Vicentić, Jelena Marjanovic and Schwirtlich, Marija and Kovačević Grujičić, Nataša and Stevanović, Milena and Drakulić, Danijela",
year = "2017",
abstract = "Glioblastoma (GBM) is one of the most aggressive and deadly forms of cancer. Literature data reveals that all-trans retinoic acid (ATRA) has anticancer effects on different types of tumor cells. However, data about the effects of ATRA on glioblastoma cells are contradictory. In this study, we examined whether ATRA treatment affects features of human glioblastoma U251 cells. To that end, the cells were treated with different concentrations of ATRA. Results obtained by MTT and the crystal violet assays imply that ATRA affected the viability of U251 glioblastoma cells in a dose-and time-dependent manner. Fluorescence staining of microtubule cytoskeleton protein a-tubulin revealed that ATRA induced changes in cell morphology. Using semi-quantitative RT-PCR we found that the expression of SOX3 and GFAP genes, as markers of neural differentiation, was not changed upon ATRA treatment. Thus, the observed changes in cell morphology after ATRA treatment are not associated with neural differentiation of U251 glioblastoma cells. The scratch-wound healing assay revealed that ATRA changed the mode of U251 cell migration from collective to single cell motility. The cell-matrix adhesion assay demonstrated that the pharmacologically relevant concentration of ATRA lowered the cell-matrix adhesion capability of U251 cells. In conclusion, our results imply that further studies are needed before ATRA could be considered for the treatment of glioblastoma.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "All-trans retinoic acid influences viability, migration and adhesion of U251 glioblastoma cells",
pages = "706-699",
number = "4",
volume = "69",
doi = "10.2298/ABS170327016M"
}
Vicentić, J. M., Schwirtlich, M., Kovačević Grujičić, N., Stevanović, M.,& Drakulić, D.. (2017). All-trans retinoic acid influences viability, migration and adhesion of U251 glioblastoma cells. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 69(4), 699-706.
https://doi.org/10.2298/ABS170327016M
Vicentić JM, Schwirtlich M, Kovačević Grujičić N, Stevanović M, Drakulić D. All-trans retinoic acid influences viability, migration and adhesion of U251 glioblastoma cells. in Archives of Biological Sciences. 2017;69(4):699-706.
doi:10.2298/ABS170327016M .
Vicentić, Jelena Marjanovic, Schwirtlich, Marija, Kovačević Grujičić, Nataša, Stevanović, Milena, Drakulić, Danijela, "All-trans retinoic acid influences viability, migration and adhesion of U251 glioblastoma cells" in Archives of Biological Sciences, 69, no. 4 (2017):699-706,
https://doi.org/10.2298/ABS170327016M . .
1
1

SOX14 activates the p53 signaling pathway and induces apoptosis in a cervical carcinoma cell line

Stanisavljević Ninković, Danijela; Petrović, Isidora; Vuković, Vladanka; Schwirtlich, Marija; Gredić, Marija; Stevanović, Milena; Popović, Jelena

(Public Library Science, San Francisco, 2017)

TY  - JOUR
AU  - Stanisavljević Ninković, Danijela
AU  - Petrović, Isidora
AU  - Vuković, Vladanka
AU  - Schwirtlich, Marija
AU  - Gredić, Marija
AU  - Stevanović, Milena
AU  - Popović, Jelena
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/996
AB  - SOX14 is a member of the SOX family of transcription factors mainly involved in the regulation of neural development. Recently, it became evident that SOX14 is one of four hyper-methylated genes in cervical carcinoma, considered as a tumor suppressor candidate in this type of malignancy. In this paper we elucidated the role of SOX14 in the regulation of malignant properties of cervical carcinoma cells in vitro. Functional analysis performed in HeLa cells revealed that SOX14 overexpression decreased viability and promoted apoptosis through altering the expression of apoptosis related genes. Our results demonstrated that overexpression of SOX14 initiated accumulation of p53, demonstrating potential cross-talk between SOX14 and the p53 signaling pathway. Further analysis unambiguously showed that SOX14 triggered posttranslational modification of p53 protein, as detected by the significantly increased level of phospho-p53 (Ser-15) in SOX14-overexpressing HeLa cells. Moreover, the obtained results revealed that SOX14 activated p53 protein, which was confirmed by elevated p21 Waf1/Cip1, a well known target gene of p53. This study advances our understanding about the role of SOX14 and might explain the molecular mechanism by which this transcription factor could exert tumor suppressor properties in cervical carcinoma.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - SOX14 activates the p53 signaling pathway and induces apoptosis in a cervical carcinoma cell line
IS  - 9
VL  - 12
DO  - 10.1371/journal.pone.0184686
ER  - 
@article{
author = "Stanisavljević Ninković, Danijela and Petrović, Isidora and Vuković, Vladanka and Schwirtlich, Marija and Gredić, Marija and Stevanović, Milena and Popović, Jelena",
year = "2017",
abstract = "SOX14 is a member of the SOX family of transcription factors mainly involved in the regulation of neural development. Recently, it became evident that SOX14 is one of four hyper-methylated genes in cervical carcinoma, considered as a tumor suppressor candidate in this type of malignancy. In this paper we elucidated the role of SOX14 in the regulation of malignant properties of cervical carcinoma cells in vitro. Functional analysis performed in HeLa cells revealed that SOX14 overexpression decreased viability and promoted apoptosis through altering the expression of apoptosis related genes. Our results demonstrated that overexpression of SOX14 initiated accumulation of p53, demonstrating potential cross-talk between SOX14 and the p53 signaling pathway. Further analysis unambiguously showed that SOX14 triggered posttranslational modification of p53 protein, as detected by the significantly increased level of phospho-p53 (Ser-15) in SOX14-overexpressing HeLa cells. Moreover, the obtained results revealed that SOX14 activated p53 protein, which was confirmed by elevated p21 Waf1/Cip1, a well known target gene of p53. This study advances our understanding about the role of SOX14 and might explain the molecular mechanism by which this transcription factor could exert tumor suppressor properties in cervical carcinoma.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "SOX14 activates the p53 signaling pathway and induces apoptosis in a cervical carcinoma cell line",
number = "9",
volume = "12",
doi = "10.1371/journal.pone.0184686"
}
Stanisavljević Ninković, D., Petrović, I., Vuković, V., Schwirtlich, M., Gredić, M., Stevanović, M.,& Popović, J.. (2017). SOX14 activates the p53 signaling pathway and induces apoptosis in a cervical carcinoma cell line. in PLoS One
Public Library Science, San Francisco., 12(9).
https://doi.org/10.1371/journal.pone.0184686
Stanisavljević Ninković D, Petrović I, Vuković V, Schwirtlich M, Gredić M, Stevanović M, Popović J. SOX14 activates the p53 signaling pathway and induces apoptosis in a cervical carcinoma cell line. in PLoS One. 2017;12(9).
doi:10.1371/journal.pone.0184686 .
Stanisavljević Ninković, Danijela, Petrović, Isidora, Vuković, Vladanka, Schwirtlich, Marija, Gredić, Marija, Stevanović, Milena, Popović, Jelena, "SOX14 activates the p53 signaling pathway and induces apoptosis in a cervical carcinoma cell line" in PLoS One, 12, no. 9 (2017),
https://doi.org/10.1371/journal.pone.0184686 . .
1
26
2
20

Epigenetic regulation of human SOX3 gene expression during early phases of neural differentiation of NT2/D1 cells

Topalović, Vladanka; Krstić, Aleksandar; Schwirtlich, Marija; Dolfini, Diletta; Mantovani, Roberto; Stevanović, Milena; Mojsin, Marija

(Public Library Science, San Francisco, 2017)

TY  - JOUR
AU  - Topalović, Vladanka
AU  - Krstić, Aleksandar
AU  - Schwirtlich, Marija
AU  - Dolfini, Diletta
AU  - Mantovani, Roberto
AU  - Stevanović, Milena
AU  - Mojsin, Marija
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1005
AB  - Sox3/SOX3 is one of the earliest neural markers in vertebrates. Together with the Sox1/SOX1 and Sox2/SOX2 genes it is implicated in the regulation of stem cell identity. In the present study, we performed the first analysis of epigenetic mechanisms (DNA methylation and histone marks) involved in the regulation of the human SOX3 gene expression during RA-induced neural differentiation of NT2/D1 cells. We show that the promoter of the human SOX3 gene is extremely hypomethylated both in undifferentiated NT2/D1 cells and during the early phases of RA-induced neural differentiation. By employing chromatin immunopre-cipitation, we analyze several histone modifications across different regions of the SOX3 gene and their dynamics following initiation of differentiation. In the same timeframe we investigate profiles of selected histone marks on the promoters of human SOX1 and SOX2 genes. We demonstrate differences in histone signatures of SOX1, SOX2 and SOX3 genes. Considering the importance of SOXB1 genes in the process of neural differentiation, the present study contributes to a better understanding of epigenetic mechanisms implicated in the regulation of pluripotency maintenance and commitment towards the neural lineage.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Epigenetic regulation of human SOX3 gene expression during early phases of neural differentiation of NT2/D1 cells
IS  - 9
VL  - 12
DO  - 10.1371/journal.pone.0184099
ER  - 
@article{
author = "Topalović, Vladanka and Krstić, Aleksandar and Schwirtlich, Marija and Dolfini, Diletta and Mantovani, Roberto and Stevanović, Milena and Mojsin, Marija",
year = "2017",
abstract = "Sox3/SOX3 is one of the earliest neural markers in vertebrates. Together with the Sox1/SOX1 and Sox2/SOX2 genes it is implicated in the regulation of stem cell identity. In the present study, we performed the first analysis of epigenetic mechanisms (DNA methylation and histone marks) involved in the regulation of the human SOX3 gene expression during RA-induced neural differentiation of NT2/D1 cells. We show that the promoter of the human SOX3 gene is extremely hypomethylated both in undifferentiated NT2/D1 cells and during the early phases of RA-induced neural differentiation. By employing chromatin immunopre-cipitation, we analyze several histone modifications across different regions of the SOX3 gene and their dynamics following initiation of differentiation. In the same timeframe we investigate profiles of selected histone marks on the promoters of human SOX1 and SOX2 genes. We demonstrate differences in histone signatures of SOX1, SOX2 and SOX3 genes. Considering the importance of SOXB1 genes in the process of neural differentiation, the present study contributes to a better understanding of epigenetic mechanisms implicated in the regulation of pluripotency maintenance and commitment towards the neural lineage.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Epigenetic regulation of human SOX3 gene expression during early phases of neural differentiation of NT2/D1 cells",
number = "9",
volume = "12",
doi = "10.1371/journal.pone.0184099"
}
Topalović, V., Krstić, A., Schwirtlich, M., Dolfini, D., Mantovani, R., Stevanović, M.,& Mojsin, M.. (2017). Epigenetic regulation of human SOX3 gene expression during early phases of neural differentiation of NT2/D1 cells. in PLoS One
Public Library Science, San Francisco., 12(9).
https://doi.org/10.1371/journal.pone.0184099
Topalović V, Krstić A, Schwirtlich M, Dolfini D, Mantovani R, Stevanović M, Mojsin M. Epigenetic regulation of human SOX3 gene expression during early phases of neural differentiation of NT2/D1 cells. in PLoS One. 2017;12(9).
doi:10.1371/journal.pone.0184099 .
Topalović, Vladanka, Krstić, Aleksandar, Schwirtlich, Marija, Dolfini, Diletta, Mantovani, Roberto, Stevanović, Milena, Mojsin, Marija, "Epigenetic regulation of human SOX3 gene expression during early phases of neural differentiation of NT2/D1 cells" in PLoS One, 12, no. 9 (2017),
https://doi.org/10.1371/journal.pone.0184099 . .
2
8
5

Histone modifications on the promoters of human OCT4 and NANOG genes at the onset of neural differentiation of NT2/D1 cells

Topalović, Vladanka; Schwirtlich, Marija; Stevanović, Milena; Mojsin, Marija

(Maik Nauka/Interperiodica/Springer, New York, 2017)

TY  - JOUR
AU  - Topalović, Vladanka
AU  - Schwirtlich, Marija
AU  - Stevanović, Milena
AU  - Mojsin, Marija
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1077
AB  - Transcription factors OCT4 and NANOG are main constituents of a functional network that controls proliferation and pluripotency maintenance of stem cells as well as early lineage decisions. We investigated expression profiles of OCT4 and NANOG during the early phases of neural differentiation using NT2/D1 cells induced by retinoic acid as an in vitro model system of human neurogenesis. We demonstrated decrease in OCT4 and NANOG mRNA and protein levels following exposure to retinoic acid. Next, by employing chromatin immunoprecipitation, we investigated profiles of selected H3 and H2B histone marks deposited on the promoters of the OCT4 and NANOG genes. We found decline in H3K4me3, H2BK5ac, and H2BK120ac on both promoters, which paralleled the decrease in OCT4 and NANOG expression. Moreover, we found that the H2BK16ac mark is differentially enriched on these two promoters, pointing to differences in epigenetic regulation of OCT4 and NANOG gene expression. Finally, based on our data, we suggest that the early response of pluripotency genes OCT4 and NANOG to the differentiation-inducing stimuli is mediated by dynamic changes in chromatin marks, while DNA methylation is acquired in the later stages of neurogenesis.
PB  - Maik Nauka/Interperiodica/Springer, New York
T2  - Biochemistry-Moscow
T1  - Histone modifications on the promoters of human OCT4 and NANOG genes at the onset of neural differentiation of NT2/D1 cells
EP  - 722
IS  - 6
SP  - 715
VL  - 82
DO  - 10.1134/S0006297917060086
ER  - 
@article{
author = "Topalović, Vladanka and Schwirtlich, Marija and Stevanović, Milena and Mojsin, Marija",
year = "2017",
abstract = "Transcription factors OCT4 and NANOG are main constituents of a functional network that controls proliferation and pluripotency maintenance of stem cells as well as early lineage decisions. We investigated expression profiles of OCT4 and NANOG during the early phases of neural differentiation using NT2/D1 cells induced by retinoic acid as an in vitro model system of human neurogenesis. We demonstrated decrease in OCT4 and NANOG mRNA and protein levels following exposure to retinoic acid. Next, by employing chromatin immunoprecipitation, we investigated profiles of selected H3 and H2B histone marks deposited on the promoters of the OCT4 and NANOG genes. We found decline in H3K4me3, H2BK5ac, and H2BK120ac on both promoters, which paralleled the decrease in OCT4 and NANOG expression. Moreover, we found that the H2BK16ac mark is differentially enriched on these two promoters, pointing to differences in epigenetic regulation of OCT4 and NANOG gene expression. Finally, based on our data, we suggest that the early response of pluripotency genes OCT4 and NANOG to the differentiation-inducing stimuli is mediated by dynamic changes in chromatin marks, while DNA methylation is acquired in the later stages of neurogenesis.",
publisher = "Maik Nauka/Interperiodica/Springer, New York",
journal = "Biochemistry-Moscow",
title = "Histone modifications on the promoters of human OCT4 and NANOG genes at the onset of neural differentiation of NT2/D1 cells",
pages = "722-715",
number = "6",
volume = "82",
doi = "10.1134/S0006297917060086"
}
Topalović, V., Schwirtlich, M., Stevanović, M.,& Mojsin, M.. (2017). Histone modifications on the promoters of human OCT4 and NANOG genes at the onset of neural differentiation of NT2/D1 cells. in Biochemistry-Moscow
Maik Nauka/Interperiodica/Springer, New York., 82(6), 715-722.
https://doi.org/10.1134/S0006297917060086
Topalović V, Schwirtlich M, Stevanović M, Mojsin M. Histone modifications on the promoters of human OCT4 and NANOG genes at the onset of neural differentiation of NT2/D1 cells. in Biochemistry-Moscow. 2017;82(6):715-722.
doi:10.1134/S0006297917060086 .
Topalović, Vladanka, Schwirtlich, Marija, Stevanović, Milena, Mojsin, Marija, "Histone modifications on the promoters of human OCT4 and NANOG genes at the onset of neural differentiation of NT2/D1 cells" in Biochemistry-Moscow, 82, no. 6 (2017):715-722,
https://doi.org/10.1134/S0006297917060086 . .
7
2
7

Crosstalk between SOXB1 proteins and WNT/beta-catenin signaling in NT2/D1 cells

Mojsin, Marija; Topalović, Vladanka; Vicentić, Jelena Marjanovic; Schwirtlich, Marija; Stanisavljević Ninković, Danijela; Drakulić, Danijela; Stevanović, Milena

(Springer, New York, 2015)

TY  - JOUR
AU  - Mojsin, Marija
AU  - Topalović, Vladanka
AU  - Vicentić, Jelena Marjanovic
AU  - Schwirtlich, Marija
AU  - Stanisavljević Ninković, Danijela
AU  - Drakulić, Danijela
AU  - Stevanović, Milena
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/840
AB  - During early vertebrate embryogenesis, the expression of SOXB1 proteins is precisely regulated by a number of different mechanisms, including Wnt/beta-catenin signaling. This is essential for controlling the balance between stemness and differentiation in embryonic stem cells. In the present study, we analyzed the molecular mechanism of LiCl action in NT2/D1 cells and examined the crosstalk between SOXB1 proteins and Wnt signaling in this model system. We have shown that LiCl increases beta-catenin level, induces its translocation to the nucleus and consequently up-regulates beta-catenin/Tcf-dependent transcription in NT2/D1 cells. Our results also suggest that LiCl treatment leads to increased expression of SOX2 and SOX3 proteins in NT2/D1 cells through activation of canonical Wnt signaling. Finally, we have detected a negative feedback loop between beta-catenin and SOX2 expression in NT2/D1 cells. Since beta-catenin and SOX2 have been linked to processes of self-renewal and pluripotency, our results have implications for future research on the maintenance of stemness and lineage commitment of embryonic stem cells.
PB  - Springer, New York
T2  - Histochemistry and Cell Biology
T1  - Crosstalk between SOXB1 proteins and WNT/beta-catenin signaling in NT2/D1 cells
EP  - 441
IS  - 5
SP  - 429
VL  - 144
DO  - 10.1007/s00418-015-1352-0
ER  - 
@article{
author = "Mojsin, Marija and Topalović, Vladanka and Vicentić, Jelena Marjanovic and Schwirtlich, Marija and Stanisavljević Ninković, Danijela and Drakulić, Danijela and Stevanović, Milena",
year = "2015",
abstract = "During early vertebrate embryogenesis, the expression of SOXB1 proteins is precisely regulated by a number of different mechanisms, including Wnt/beta-catenin signaling. This is essential for controlling the balance between stemness and differentiation in embryonic stem cells. In the present study, we analyzed the molecular mechanism of LiCl action in NT2/D1 cells and examined the crosstalk between SOXB1 proteins and Wnt signaling in this model system. We have shown that LiCl increases beta-catenin level, induces its translocation to the nucleus and consequently up-regulates beta-catenin/Tcf-dependent transcription in NT2/D1 cells. Our results also suggest that LiCl treatment leads to increased expression of SOX2 and SOX3 proteins in NT2/D1 cells through activation of canonical Wnt signaling. Finally, we have detected a negative feedback loop between beta-catenin and SOX2 expression in NT2/D1 cells. Since beta-catenin and SOX2 have been linked to processes of self-renewal and pluripotency, our results have implications for future research on the maintenance of stemness and lineage commitment of embryonic stem cells.",
publisher = "Springer, New York",
journal = "Histochemistry and Cell Biology",
title = "Crosstalk between SOXB1 proteins and WNT/beta-catenin signaling in NT2/D1 cells",
pages = "441-429",
number = "5",
volume = "144",
doi = "10.1007/s00418-015-1352-0"
}
Mojsin, M., Topalović, V., Vicentić, J. M., Schwirtlich, M., Stanisavljević Ninković, D., Drakulić, D.,& Stevanović, M.. (2015). Crosstalk between SOXB1 proteins and WNT/beta-catenin signaling in NT2/D1 cells. in Histochemistry and Cell Biology
Springer, New York., 144(5), 429-441.
https://doi.org/10.1007/s00418-015-1352-0
Mojsin M, Topalović V, Vicentić JM, Schwirtlich M, Stanisavljević Ninković D, Drakulić D, Stevanović M. Crosstalk between SOXB1 proteins and WNT/beta-catenin signaling in NT2/D1 cells. in Histochemistry and Cell Biology. 2015;144(5):429-441.
doi:10.1007/s00418-015-1352-0 .
Mojsin, Marija, Topalović, Vladanka, Vicentić, Jelena Marjanovic, Schwirtlich, Marija, Stanisavljević Ninković, Danijela, Drakulić, Danijela, Stevanović, Milena, "Crosstalk between SOXB1 proteins and WNT/beta-catenin signaling in NT2/D1 cells" in Histochemistry and Cell Biology, 144, no. 5 (2015):429-441,
https://doi.org/10.1007/s00418-015-1352-0 . .
1
5
4
5

SOX18 Is a Novel Target Gene of Hedgehog Signaling in Cervical Carcinoma Cell Lines

Petrović, Isidora; Milivojević, Milena; Popović, Jelena; Schwirtlich, Marija; Ranković, Branislava; Stevanović, Milena

(Public Library Science, San Francisco, 2015)

TY  - JOUR
AU  - Petrović, Isidora
AU  - Milivojević, Milena
AU  - Popović, Jelena
AU  - Schwirtlich, Marija
AU  - Ranković, Branislava
AU  - Stevanović, Milena
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/836
AB  - Although there is much evidence showing functional relationship between Hedgehog pathway, in particular Sonic hedgehog, and SOX transcription factors during embryonic development, scarce data are available regarding their crosstalk in cancer cells. SOX18 protein plays an important role in promoting tumor angiogenesis and therefore emerged as a promising potential target in antiangiogenic tumor therapy. Recently it became evident that expression of SOX18 gene in tumors is not restricted to endothelium of accompanying blood and lymphatic vessels, but in tumor cells as well. In this paper we have identified human SOX18 gene as a novel target gene of Hedgehog signaling in cervical carcinoma cell lines. We have presented data showing that expression of SOX18 gene is regulated by GLI1 and GLI2 transcription factors, final effectors of Hedgehog signaling, and that modulation of Hedgehog signaling activity in considerably influence SOX18 expression. We consider important that Hedgehog pathway inhibitors reduced SOX18 expression, thus showing, for the first time, possibility for manipulationwith SOX18 gene expression. In addition, we analyzed the role of SOX18 in malignant potential of cervical carcinoma cell line, and showed that its overexpression has no influence on cells proliferation and viability, but substantially promotes migration and invasion of cells in vitro. Pro-migratory effect of SOX18 suggests its role in promoting malignant spreading, possibly in response to Hedgehog activation.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - SOX18 Is a Novel Target Gene of Hedgehog Signaling in Cervical Carcinoma Cell Lines
IS  - 11
VL  - 10
DO  - 10.1371/journal.pone.0143591
ER  - 
@article{
author = "Petrović, Isidora and Milivojević, Milena and Popović, Jelena and Schwirtlich, Marija and Ranković, Branislava and Stevanović, Milena",
year = "2015",
abstract = "Although there is much evidence showing functional relationship between Hedgehog pathway, in particular Sonic hedgehog, and SOX transcription factors during embryonic development, scarce data are available regarding their crosstalk in cancer cells. SOX18 protein plays an important role in promoting tumor angiogenesis and therefore emerged as a promising potential target in antiangiogenic tumor therapy. Recently it became evident that expression of SOX18 gene in tumors is not restricted to endothelium of accompanying blood and lymphatic vessels, but in tumor cells as well. In this paper we have identified human SOX18 gene as a novel target gene of Hedgehog signaling in cervical carcinoma cell lines. We have presented data showing that expression of SOX18 gene is regulated by GLI1 and GLI2 transcription factors, final effectors of Hedgehog signaling, and that modulation of Hedgehog signaling activity in considerably influence SOX18 expression. We consider important that Hedgehog pathway inhibitors reduced SOX18 expression, thus showing, for the first time, possibility for manipulationwith SOX18 gene expression. In addition, we analyzed the role of SOX18 in malignant potential of cervical carcinoma cell line, and showed that its overexpression has no influence on cells proliferation and viability, but substantially promotes migration and invasion of cells in vitro. Pro-migratory effect of SOX18 suggests its role in promoting malignant spreading, possibly in response to Hedgehog activation.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "SOX18 Is a Novel Target Gene of Hedgehog Signaling in Cervical Carcinoma Cell Lines",
number = "11",
volume = "10",
doi = "10.1371/journal.pone.0143591"
}
Petrović, I., Milivojević, M., Popović, J., Schwirtlich, M., Ranković, B.,& Stevanović, M.. (2015). SOX18 Is a Novel Target Gene of Hedgehog Signaling in Cervical Carcinoma Cell Lines. in PLoS One
Public Library Science, San Francisco., 10(11).
https://doi.org/10.1371/journal.pone.0143591
Petrović I, Milivojević M, Popović J, Schwirtlich M, Ranković B, Stevanović M. SOX18 Is a Novel Target Gene of Hedgehog Signaling in Cervical Carcinoma Cell Lines. in PLoS One. 2015;10(11).
doi:10.1371/journal.pone.0143591 .
Petrović, Isidora, Milivojević, Milena, Popović, Jelena, Schwirtlich, Marija, Ranković, Branislava, Stevanović, Milena, "SOX18 Is a Novel Target Gene of Hedgehog Signaling in Cervical Carcinoma Cell Lines" in PLoS One, 10, no. 11 (2015),
https://doi.org/10.1371/journal.pone.0143591 . .
5
24
11
27

The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1

Drakulić, Danijela; Vicentić, Jelena Marjanovic; Schwirtlich, Marija; Tosić, Jelena; Krstić, Aleksandar; Lazić, Andrijana; Stevanović, Milena

(Acad Brasileira De Ciencias, Rio Janeiro, 2015)

TY  - JOUR
AU  - Drakulić, Danijela
AU  - Vicentić, Jelena Marjanovic
AU  - Schwirtlich, Marija
AU  - Tosić, Jelena
AU  - Krstić, Aleksandar
AU  - Lazić, Andrijana
AU  - Stevanović, Milena
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/889
AB  - The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor. We detected that increased SOX2 expression changed the speed, mode and path of cell migration, but not the adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2 overexpression increased the expression of the tumor suppressor protein p53 and the HDM2 oncogene. Our results contribute to the better understanding of the effect of SOX2 on the behavior of tumor cells originating from a human testicular germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many features, our results could contribute to the elucidation of the role of SOX2 in cancer stem cells behavior and the process of metastasis.
PB  - Acad Brasileira De Ciencias, Rio Janeiro
T2  - Anais da Academia Brasileira de Ciencias
T1  - The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1
EP  - 405
IS  - 1
SP  - 389
VL  - 87
DO  - 10.1590/0001-3765201520140352
ER  - 
@article{
author = "Drakulić, Danijela and Vicentić, Jelena Marjanovic and Schwirtlich, Marija and Tosić, Jelena and Krstić, Aleksandar and Lazić, Andrijana and Stevanović, Milena",
year = "2015",
abstract = "The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor. We detected that increased SOX2 expression changed the speed, mode and path of cell migration, but not the adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2 overexpression increased the expression of the tumor suppressor protein p53 and the HDM2 oncogene. Our results contribute to the better understanding of the effect of SOX2 on the behavior of tumor cells originating from a human testicular germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many features, our results could contribute to the elucidation of the role of SOX2 in cancer stem cells behavior and the process of metastasis.",
publisher = "Acad Brasileira De Ciencias, Rio Janeiro",
journal = "Anais da Academia Brasileira de Ciencias",
title = "The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1",
pages = "405-389",
number = "1",
volume = "87",
doi = "10.1590/0001-3765201520140352"
}
Drakulić, D., Vicentić, J. M., Schwirtlich, M., Tosić, J., Krstić, A., Lazić, A.,& Stevanović, M.. (2015). The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1. in Anais da Academia Brasileira de Ciencias
Acad Brasileira De Ciencias, Rio Janeiro., 87(1), 389-405.
https://doi.org/10.1590/0001-3765201520140352
Drakulić D, Vicentić JM, Schwirtlich M, Tosić J, Krstić A, Lazić A, Stevanović M. The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1. in Anais da Academia Brasileira de Ciencias. 2015;87(1):389-405.
doi:10.1590/0001-3765201520140352 .
Drakulić, Danijela, Vicentić, Jelena Marjanovic, Schwirtlich, Marija, Tosić, Jelena, Krstić, Aleksandar, Lazić, Andrijana, Stevanović, Milena, "The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1" in Anais da Academia Brasileira de Ciencias, 87, no. 1 (2015):389-405,
https://doi.org/10.1590/0001-3765201520140352 . .
9
2
9

The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons

Vastagh, Csaba; Schwirtlich, Marija; Kwakowsky, Andrea; Erdelyi, Ferenc; Margolis, Frank L.; Yanagawa, Yuchio; Katarova, Zoya; Szabo, Gabor

(Wiley, Hoboken, 2015)

TY  - JOUR
AU  - Vastagh, Csaba
AU  - Schwirtlich, Marija
AU  - Kwakowsky, Andrea
AU  - Erdelyi, Ferenc
AU  - Margolis, Frank L.
AU  - Yanagawa, Yuchio
AU  - Katarova, Zoya
AU  - Szabo, Gabor
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/898
AB  - Gamma-aminobutyric acid (GABA) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 coexpressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually nonoverlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia In contrast GAD67 is expressed in a subregion of the nonsensory epithelium/vomeronasal organ epithelium containing the putative Gonadotropin-releasing hormone (GnRH) progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant embryonic GAD (EGAD) concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and postmigratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock-out embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools.
PB  - Wiley, Hoboken
T2  - Developmental Neurobiology
T1  - The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons
EP  - 270
IS  - 3
SP  - 249
VL  - 75
DO  - 10.1002/dneu.22222
ER  - 
@article{
author = "Vastagh, Csaba and Schwirtlich, Marija and Kwakowsky, Andrea and Erdelyi, Ferenc and Margolis, Frank L. and Yanagawa, Yuchio and Katarova, Zoya and Szabo, Gabor",
year = "2015",
abstract = "Gamma-aminobutyric acid (GABA) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 coexpressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually nonoverlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia In contrast GAD67 is expressed in a subregion of the nonsensory epithelium/vomeronasal organ epithelium containing the putative Gonadotropin-releasing hormone (GnRH) progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant embryonic GAD (EGAD) concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and postmigratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock-out embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools.",
publisher = "Wiley, Hoboken",
journal = "Developmental Neurobiology",
title = "The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons",
pages = "270-249",
number = "3",
volume = "75",
doi = "10.1002/dneu.22222"
}
Vastagh, C., Schwirtlich, M., Kwakowsky, A., Erdelyi, F., Margolis, F. L., Yanagawa, Y., Katarova, Z.,& Szabo, G.. (2015). The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons. in Developmental Neurobiology
Wiley, Hoboken., 75(3), 249-270.
https://doi.org/10.1002/dneu.22222
Vastagh C, Schwirtlich M, Kwakowsky A, Erdelyi F, Margolis FL, Yanagawa Y, Katarova Z, Szabo G. The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons. in Developmental Neurobiology. 2015;75(3):249-270.
doi:10.1002/dneu.22222 .
Vastagh, Csaba, Schwirtlich, Marija, Kwakowsky, Andrea, Erdelyi, Ferenc, Margolis, Frank L., Yanagawa, Yuchio, Katarova, Zoya, Szabo, Gabor, "The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons" in Developmental Neurobiology, 75, no. 3 (2015):249-270,
https://doi.org/10.1002/dneu.22222 . .
7
1
5

Quercetin reduces pluripotency, migration and adhesion of human teratocarcinoma cell line NT2/D1 by inhibiting Wnt/beta-catenin signaling

Mojsin, Marija; Vicentić, Jelena Marjanovic; Schwirtlich, Marija; Topalović, Vladanka; Stevanović, Milena

(Royal Soc Chemistry, Cambridge, 2014)

TY  - JOUR
AU  - Mojsin, Marija
AU  - Vicentić, Jelena Marjanovic
AU  - Schwirtlich, Marija
AU  - Topalović, Vladanka
AU  - Stevanović, Milena
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/743
AB  - Quercetin, a bioflavonoid found in plant foods, has a wide range of therapeutic effects. In order to examine the therapeutic potential of quercetin in teratocarcinoma, we used the human teratocarcinoma cell line NT2/D1 as an in vitro model. We have shown that quercetin inhibits the proliferation, adhesion and migration of NT2/D1 cells and downregulates the expression of pluripotency factors SOX2, Oct4 and Nanog. Our results further suggest that the anticancer effect of quercetin against human teratocarcinoma cells is mediated by targeting the canonical Wnt signaling pathway. Quercetin antagonized the Wnt/beta-catenin signaling pathway in NT2/D1 cells by inhibiting beta-catenin nuclear translocation and the consequent downregulation of beta-catenin-dependent transcription. These data suggest that quercetin as a potent inhibitor of Wnt signaling may be an effective therapeutic agent in cancers with aberrant activation of the Wnt pathway.
PB  - Royal Soc Chemistry, Cambridge
T2  - Food & Function
T1  - Quercetin reduces pluripotency, migration and adhesion of human teratocarcinoma cell line NT2/D1 by inhibiting Wnt/beta-catenin signaling
EP  - 2573
IS  - 10
SP  - 2564
VL  - 5
DO  - 10.1039/c4fo00484a
ER  - 
@article{
author = "Mojsin, Marija and Vicentić, Jelena Marjanovic and Schwirtlich, Marija and Topalović, Vladanka and Stevanović, Milena",
year = "2014",
abstract = "Quercetin, a bioflavonoid found in plant foods, has a wide range of therapeutic effects. In order to examine the therapeutic potential of quercetin in teratocarcinoma, we used the human teratocarcinoma cell line NT2/D1 as an in vitro model. We have shown that quercetin inhibits the proliferation, adhesion and migration of NT2/D1 cells and downregulates the expression of pluripotency factors SOX2, Oct4 and Nanog. Our results further suggest that the anticancer effect of quercetin against human teratocarcinoma cells is mediated by targeting the canonical Wnt signaling pathway. Quercetin antagonized the Wnt/beta-catenin signaling pathway in NT2/D1 cells by inhibiting beta-catenin nuclear translocation and the consequent downregulation of beta-catenin-dependent transcription. These data suggest that quercetin as a potent inhibitor of Wnt signaling may be an effective therapeutic agent in cancers with aberrant activation of the Wnt pathway.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Food & Function",
title = "Quercetin reduces pluripotency, migration and adhesion of human teratocarcinoma cell line NT2/D1 by inhibiting Wnt/beta-catenin signaling",
pages = "2573-2564",
number = "10",
volume = "5",
doi = "10.1039/c4fo00484a"
}
Mojsin, M., Vicentić, J. M., Schwirtlich, M., Topalović, V.,& Stevanović, M.. (2014). Quercetin reduces pluripotency, migration and adhesion of human teratocarcinoma cell line NT2/D1 by inhibiting Wnt/beta-catenin signaling. in Food & Function
Royal Soc Chemistry, Cambridge., 5(10), 2564-2573.
https://doi.org/10.1039/c4fo00484a
Mojsin M, Vicentić JM, Schwirtlich M, Topalović V, Stevanović M. Quercetin reduces pluripotency, migration and adhesion of human teratocarcinoma cell line NT2/D1 by inhibiting Wnt/beta-catenin signaling. in Food & Function. 2014;5(10):2564-2573.
doi:10.1039/c4fo00484a .
Mojsin, Marija, Vicentić, Jelena Marjanovic, Schwirtlich, Marija, Topalović, Vladanka, Stevanović, Milena, "Quercetin reduces pluripotency, migration and adhesion of human teratocarcinoma cell line NT2/D1 by inhibiting Wnt/beta-catenin signaling" in Food & Function, 5, no. 10 (2014):2564-2573,
https://doi.org/10.1039/c4fo00484a . .
1
25
10
30

SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells

Klajn, Andrijana; Drakulić, Danijela; Tosić, M.; Pavković, Z.; Schwirtlich, Marija; Stevanović, Milena

(Maik Nauka/Interperiodica/Springer, New York, 2014)

TY  - JOUR
AU  - Klajn, Andrijana
AU  - Drakulić, Danijela
AU  - Tosić, M.
AU  - Pavković, Z.
AU  - Schwirtlich, Marija
AU  - Stevanović, Milena
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/735
AB  - SOX2 is one of the key transcription factors involved in maintenance of neural progenitor identity. However, its function during the process of neural differentiation, including phases of lineage-specification and terminal differentiation, is still poorly understood. Considering growing evidence indicating that SOX2 expression level must be tightly controlled for proper neural development, the aim of this research was to analyze the effects of constitutive SOX2 overexpression on outcome of retinoic acid-induced neural differentiation of pluripotent NT2/D1 cells. We demonstrated that in spite of constitutive SOX2 overexpression, NT2/D1 cells were able to reach final phases of neural differentiation yielding both neuronal and glial cells. However, SOX2 overexpression reduced the number of mature MAP2-positive neurons while no difference in the number of GFAP-positive astrocytes was detected. In-depth analysis at single-cell level showed that SOX2 downregulation was in correlation with both neuronal and glial phenotype acquisitions. Interestingly, while in mature neurons SOX2 was completely downregulated, astrocytes with low level of SOX2 expression were detected. Nevertheless, cells with high level of SOX2 expression were incapable of entering in either of two differentiation pathways, neurogenesis or gliogenesis. Accordingly, our results indicate that fine balance between undifferentiated state and neural differentiation depends on SOX2 expression level. Unlike neurons, astrocytes could maintain low level of SOX2 expression after they acquired glial fate. Further studies are needed to determine whether differences in the level of SOX2 expression in GFAP-positive astrocytes are in correlation with their self-renewal capacity, differentiation status, and/or their phenotypic characteristics.
PB  - Maik Nauka/Interperiodica/Springer, New York
T2  - Biochemistry-Moscow
T1  - SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells
EP  - 1182
IS  - 11
SP  - 1172
VL  - 79
DO  - 10.1134/S0006297914110042
ER  - 
@article{
author = "Klajn, Andrijana and Drakulić, Danijela and Tosić, M. and Pavković, Z. and Schwirtlich, Marija and Stevanović, Milena",
year = "2014",
abstract = "SOX2 is one of the key transcription factors involved in maintenance of neural progenitor identity. However, its function during the process of neural differentiation, including phases of lineage-specification and terminal differentiation, is still poorly understood. Considering growing evidence indicating that SOX2 expression level must be tightly controlled for proper neural development, the aim of this research was to analyze the effects of constitutive SOX2 overexpression on outcome of retinoic acid-induced neural differentiation of pluripotent NT2/D1 cells. We demonstrated that in spite of constitutive SOX2 overexpression, NT2/D1 cells were able to reach final phases of neural differentiation yielding both neuronal and glial cells. However, SOX2 overexpression reduced the number of mature MAP2-positive neurons while no difference in the number of GFAP-positive astrocytes was detected. In-depth analysis at single-cell level showed that SOX2 downregulation was in correlation with both neuronal and glial phenotype acquisitions. Interestingly, while in mature neurons SOX2 was completely downregulated, astrocytes with low level of SOX2 expression were detected. Nevertheless, cells with high level of SOX2 expression were incapable of entering in either of two differentiation pathways, neurogenesis or gliogenesis. Accordingly, our results indicate that fine balance between undifferentiated state and neural differentiation depends on SOX2 expression level. Unlike neurons, astrocytes could maintain low level of SOX2 expression after they acquired glial fate. Further studies are needed to determine whether differences in the level of SOX2 expression in GFAP-positive astrocytes are in correlation with their self-renewal capacity, differentiation status, and/or their phenotypic characteristics.",
publisher = "Maik Nauka/Interperiodica/Springer, New York",
journal = "Biochemistry-Moscow",
title = "SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells",
pages = "1182-1172",
number = "11",
volume = "79",
doi = "10.1134/S0006297914110042"
}
Klajn, A., Drakulić, D., Tosić, M., Pavković, Z., Schwirtlich, M.,& Stevanović, M.. (2014). SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells. in Biochemistry-Moscow
Maik Nauka/Interperiodica/Springer, New York., 79(11), 1172-1182.
https://doi.org/10.1134/S0006297914110042
Klajn A, Drakulić D, Tosić M, Pavković Z, Schwirtlich M, Stevanović M. SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells. in Biochemistry-Moscow. 2014;79(11):1172-1182.
doi:10.1134/S0006297914110042 .
Klajn, Andrijana, Drakulić, Danijela, Tosić, M., Pavković, Z., Schwirtlich, Marija, Stevanović, Milena, "SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells" in Biochemistry-Moscow, 79, no. 11 (2014):1172-1182,
https://doi.org/10.1134/S0006297914110042 . .
11
3
8

Expression Analysis of SOX14 during Retinoic Acid Induced Neural Differentiation of Embryonal Carcinoma Cells and Assessment of the Effect of Its Ectopic Expression on SOXB Members in HeLa Cells

Popović, Jelena; Stanisavljević Ninković, Danijela; Schwirtlich, Marija; Lazić, Andrijana; Marjanović, Jelena; Stevanović, Milena

(Public Library Science, San Francisco, 2014)

TY  - JOUR
AU  - Popović, Jelena
AU  - Stanisavljević Ninković, Danijela
AU  - Schwirtlich, Marija
AU  - Lazić, Andrijana
AU  - Marjanović, Jelena
AU  - Stevanović, Milena
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/785
AB  - SOX14 is a member of the SOXB2 subgroup of transcription factors implicated in neural development. Although the first SOX14 gene in vertebrates was cloned and characterized more than a decade ago and its expression profile during development was revealed in various animal model systems, the role of this gene during neural development is largely unknown. In the present study we analyzed the expression of SOX14 in human NT2/D1 and mouse P19 pluripotent embryonal carcinoma cells. We demonstrated that it is expressed in both cell lines and upregulated during retinoic acid induced neural differentiation. We showed that SOX14 was expressed in both neuronal and non-neuronal differentiated derivatives, as revealed by immunocytochemistry. Since it was previously proposed that increased SOXB2 proteins level interfere with the activity of SOXB1 counteracting partners, we compared expression patterns of SOXB members during retinoic acid induction of embryonal carcinoma cells. We revealed that upregulation of SOX14 expression is accompanied by alterations in the expression patterns of SOXB1 members. In order to analyze the potential cross-talk between them, we generated SOX14 expression construct. The ectopic expression of SOX14 was demonstrated at the mRNA level in NT2/D1, P19 and HeLa cells, while an increased level of SOX14 protein was detected in HeLa cells only. By transient transfection experiments in HeLa cells we showed for the first time that ectopic expression of SOX14 repressed SOX1 expression, whereas no significant effect on SOX2, SOX3 and SOX21 was observed. Data presented here provide an insight into SOX14 expression during in vitro neural differentiation of embryonal carcinoma cells and demonstrate the effect of its ectopic expression on protein levels of SOXB members in HeLa cells. Obtained results contribute to better understanding the role of one of the most conserved SOX proteins.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Expression Analysis of SOX14 during Retinoic Acid Induced Neural Differentiation of Embryonal Carcinoma Cells and Assessment of the Effect of Its Ectopic Expression on SOXB Members in HeLa Cells
IS  - 3
VL  - 9
DO  - 10.1371/journal.pone.0091852
ER  - 
@article{
author = "Popović, Jelena and Stanisavljević Ninković, Danijela and Schwirtlich, Marija and Lazić, Andrijana and Marjanović, Jelena and Stevanović, Milena",
year = "2014",
abstract = "SOX14 is a member of the SOXB2 subgroup of transcription factors implicated in neural development. Although the first SOX14 gene in vertebrates was cloned and characterized more than a decade ago and its expression profile during development was revealed in various animal model systems, the role of this gene during neural development is largely unknown. In the present study we analyzed the expression of SOX14 in human NT2/D1 and mouse P19 pluripotent embryonal carcinoma cells. We demonstrated that it is expressed in both cell lines and upregulated during retinoic acid induced neural differentiation. We showed that SOX14 was expressed in both neuronal and non-neuronal differentiated derivatives, as revealed by immunocytochemistry. Since it was previously proposed that increased SOXB2 proteins level interfere with the activity of SOXB1 counteracting partners, we compared expression patterns of SOXB members during retinoic acid induction of embryonal carcinoma cells. We revealed that upregulation of SOX14 expression is accompanied by alterations in the expression patterns of SOXB1 members. In order to analyze the potential cross-talk between them, we generated SOX14 expression construct. The ectopic expression of SOX14 was demonstrated at the mRNA level in NT2/D1, P19 and HeLa cells, while an increased level of SOX14 protein was detected in HeLa cells only. By transient transfection experiments in HeLa cells we showed for the first time that ectopic expression of SOX14 repressed SOX1 expression, whereas no significant effect on SOX2, SOX3 and SOX21 was observed. Data presented here provide an insight into SOX14 expression during in vitro neural differentiation of embryonal carcinoma cells and demonstrate the effect of its ectopic expression on protein levels of SOXB members in HeLa cells. Obtained results contribute to better understanding the role of one of the most conserved SOX proteins.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Expression Analysis of SOX14 during Retinoic Acid Induced Neural Differentiation of Embryonal Carcinoma Cells and Assessment of the Effect of Its Ectopic Expression on SOXB Members in HeLa Cells",
number = "3",
volume = "9",
doi = "10.1371/journal.pone.0091852"
}
Popović, J., Stanisavljević Ninković, D., Schwirtlich, M., Lazić, A., Marjanović, J.,& Stevanović, M.. (2014). Expression Analysis of SOX14 during Retinoic Acid Induced Neural Differentiation of Embryonal Carcinoma Cells and Assessment of the Effect of Its Ectopic Expression on SOXB Members in HeLa Cells. in PLoS One
Public Library Science, San Francisco., 9(3).
https://doi.org/10.1371/journal.pone.0091852
Popović J, Stanisavljević Ninković D, Schwirtlich M, Lazić A, Marjanović J, Stevanović M. Expression Analysis of SOX14 during Retinoic Acid Induced Neural Differentiation of Embryonal Carcinoma Cells and Assessment of the Effect of Its Ectopic Expression on SOXB Members in HeLa Cells. in PLoS One. 2014;9(3).
doi:10.1371/journal.pone.0091852 .
Popović, Jelena, Stanisavljević Ninković, Danijela, Schwirtlich, Marija, Lazić, Andrijana, Marjanović, Jelena, Stevanović, Milena, "Expression Analysis of SOX14 during Retinoic Acid Induced Neural Differentiation of Embryonal Carcinoma Cells and Assessment of the Effect of Its Ectopic Expression on SOXB Members in HeLa Cells" in PLoS One, 9, no. 3 (2014),
https://doi.org/10.1371/journal.pone.0091852 . .
34
18
29

SOX14 downregulates SOX1 expression in HeLa cells

Petrović, Isidora; Popović, Jelena; Stanisavljević Ninković, Danijela; Schwirtlich, Marija; Klajn, Andrijana; Marjanović, J.; Kovačević Grujičić, Nataša; Topalović, Vladanka; Mojsin, Marija; Stevanović, Milena

(Elsevier Sci Ltd, Oxford, 2014)

TY  - CONF
AU  - Petrović, Isidora
AU  - Popović, Jelena
AU  - Stanisavljević Ninković, Danijela
AU  - Schwirtlich, Marija
AU  - Klajn, Andrijana
AU  - Marjanović, J.
AU  - Kovačević Grujičić, Nataša
AU  - Topalović, Vladanka
AU  - Mojsin, Marija
AU  - Stevanović, Milena
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/731
PB  - Elsevier Sci Ltd, Oxford
C3  - European Journal of Cancer
T1  - SOX14 downregulates SOX1 expression in HeLa cells
EP  - S56
SP  - S56
VL  - 50
DO  - 10.1016/S0959-8049(14)50210-9
ER  - 
@conference{
author = "Petrović, Isidora and Popović, Jelena and Stanisavljević Ninković, Danijela and Schwirtlich, Marija and Klajn, Andrijana and Marjanović, J. and Kovačević Grujičić, Nataša and Topalović, Vladanka and Mojsin, Marija and Stevanović, Milena",
year = "2014",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "European Journal of Cancer",
title = "SOX14 downregulates SOX1 expression in HeLa cells",
pages = "S56-S56",
volume = "50",
doi = "10.1016/S0959-8049(14)50210-9"
}
Petrović, I., Popović, J., Stanisavljević Ninković, D., Schwirtlich, M., Klajn, A., Marjanović, J., Kovačević Grujičić, N., Topalović, V., Mojsin, M.,& Stevanović, M.. (2014). SOX14 downregulates SOX1 expression in HeLa cells. in European Journal of Cancer
Elsevier Sci Ltd, Oxford., 50, S56-S56.
https://doi.org/10.1016/S0959-8049(14)50210-9
Petrović I, Popović J, Stanisavljević Ninković D, Schwirtlich M, Klajn A, Marjanović J, Kovačević Grujičić N, Topalović V, Mojsin M, Stevanović M. SOX14 downregulates SOX1 expression in HeLa cells. in European Journal of Cancer. 2014;50:S56-S56.
doi:10.1016/S0959-8049(14)50210-9 .
Petrović, Isidora, Popović, Jelena, Stanisavljević Ninković, Danijela, Schwirtlich, Marija, Klajn, Andrijana, Marjanović, J., Kovačević Grujičić, Nataša, Topalović, Vladanka, Mojsin, Marija, Stevanović, Milena, "SOX14 downregulates SOX1 expression in HeLa cells" in European Journal of Cancer, 50 (2014):S56-S56,
https://doi.org/10.1016/S0959-8049(14)50210-9 . .

GABAergic signaling in primary lens epithelial and lentoid cells and its involvement in intracellular Ca2+ modulation

Schwirtlich, Marija; Kwakowsky, Andrea; Emri, Zsuzsa; Antal, Karoly; Lacza, Zsombor; Cselenyak, Attila; Katarova, Zoya; Szabo, Gabor

(Elsevier Sci Ltd, Oxford, 2011)

TY  - JOUR
AU  - Schwirtlich, Marija
AU  - Kwakowsky, Andrea
AU  - Emri, Zsuzsa
AU  - Antal, Karoly
AU  - Lacza, Zsombor
AU  - Cselenyak, Attila
AU  - Katarova, Zoya
AU  - Szabo, Gabor
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/490
AB  - Primary lens epithelial cell (LEC) cultures derived from newborn (P0) and one-month-old (P30) mouse lenses were used to study GABA (gamma-aminobutyric acid) signaling expression and its effect on the intracellular Ca2+ ([Ca2+](i)) level. We have found that these cultures express specific cellular markers for lens epithelial and fiber cells, all components of the functional GABA signaling pathway and GABA, thus recapitulating the developmental program of the ocular lens. Activation of both GABA-A and GABA-B receptors (GABA(A)R and GABA(B)R) with the specific agonists muscimol and baclofen, respectively induces [Ca2+](i) transients that could be blocked by the specific antagonists bicuculline and CGP55845 and were dependent on extracellular Ca2+. Bicuculline did not change the GABA-evoked Ca2+ responses in Ca-2-containing buffers, but suppressed them significantly in Ca2+-free buffers suggesting the two receptors couple to convergent Ca2+ mobilization mechanisms with different extracellular Ca2+ sensitivity. Prolonged activation of GABA(B)R induced wave propagation of the Ca2+ signal and persistent oscillations. The number of cells reacting to GABA or GABA + bicuculline in P30 mouse LEC cultures expressing predominantly the synaptic type GABA(A)R did not differ significantly from the number of reacting cells in PO mouse LEC cultures. The GABA-induced Ca2+ transients in P30 (but not P0) mouse LEC could be entirely suppressed by co-application of bicuculline and CGP55845. The GABA-mediated Ca2+ signaling may be involved in a variety of Ca2+-dependent cellular processes during lens growth and epithelial cell differentiation.
PB  - Elsevier Sci Ltd, Oxford
T2  - Cell Calcium
T1  - GABAergic signaling in primary lens epithelial and lentoid cells and its involvement in intracellular Ca2+ modulation
EP  - 392
IS  - 4
SP  - 381
VL  - 50
DO  - 10.1016/j.ceca.2011.07.002
ER  - 
@article{
author = "Schwirtlich, Marija and Kwakowsky, Andrea and Emri, Zsuzsa and Antal, Karoly and Lacza, Zsombor and Cselenyak, Attila and Katarova, Zoya and Szabo, Gabor",
year = "2011",
abstract = "Primary lens epithelial cell (LEC) cultures derived from newborn (P0) and one-month-old (P30) mouse lenses were used to study GABA (gamma-aminobutyric acid) signaling expression and its effect on the intracellular Ca2+ ([Ca2+](i)) level. We have found that these cultures express specific cellular markers for lens epithelial and fiber cells, all components of the functional GABA signaling pathway and GABA, thus recapitulating the developmental program of the ocular lens. Activation of both GABA-A and GABA-B receptors (GABA(A)R and GABA(B)R) with the specific agonists muscimol and baclofen, respectively induces [Ca2+](i) transients that could be blocked by the specific antagonists bicuculline and CGP55845 and were dependent on extracellular Ca2+. Bicuculline did not change the GABA-evoked Ca2+ responses in Ca-2-containing buffers, but suppressed them significantly in Ca2+-free buffers suggesting the two receptors couple to convergent Ca2+ mobilization mechanisms with different extracellular Ca2+ sensitivity. Prolonged activation of GABA(B)R induced wave propagation of the Ca2+ signal and persistent oscillations. The number of cells reacting to GABA or GABA + bicuculline in P30 mouse LEC cultures expressing predominantly the synaptic type GABA(A)R did not differ significantly from the number of reacting cells in PO mouse LEC cultures. The GABA-induced Ca2+ transients in P30 (but not P0) mouse LEC could be entirely suppressed by co-application of bicuculline and CGP55845. The GABA-mediated Ca2+ signaling may be involved in a variety of Ca2+-dependent cellular processes during lens growth and epithelial cell differentiation.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Cell Calcium",
title = "GABAergic signaling in primary lens epithelial and lentoid cells and its involvement in intracellular Ca2+ modulation",
pages = "392-381",
number = "4",
volume = "50",
doi = "10.1016/j.ceca.2011.07.002"
}
Schwirtlich, M., Kwakowsky, A., Emri, Z., Antal, K., Lacza, Z., Cselenyak, A., Katarova, Z.,& Szabo, G.. (2011). GABAergic signaling in primary lens epithelial and lentoid cells and its involvement in intracellular Ca2+ modulation. in Cell Calcium
Elsevier Sci Ltd, Oxford., 50(4), 381-392.
https://doi.org/10.1016/j.ceca.2011.07.002
Schwirtlich M, Kwakowsky A, Emri Z, Antal K, Lacza Z, Cselenyak A, Katarova Z, Szabo G. GABAergic signaling in primary lens epithelial and lentoid cells and its involvement in intracellular Ca2+ modulation. in Cell Calcium. 2011;50(4):381-392.
doi:10.1016/j.ceca.2011.07.002 .
Schwirtlich, Marija, Kwakowsky, Andrea, Emri, Zsuzsa, Antal, Karoly, Lacza, Zsombor, Cselenyak, Attila, Katarova, Zoya, Szabo, Gabor, "GABAergic signaling in primary lens epithelial and lentoid cells and its involvement in intracellular Ca2+ modulation" in Cell Calcium, 50, no. 4 (2011):381-392,
https://doi.org/10.1016/j.ceca.2011.07.002 . .
6
6

GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+

Schwirtlich, Marija; Emri, Zsuzsa; Antal, Karoly; Mate, Zoltan; Katarova, Zoya; Szabo, Gabor

(Federation Amer Soc Exp Biol, Bethesda, 2010)

TY  - JOUR
AU  - Schwirtlich, Marija
AU  - Emri, Zsuzsa
AU  - Antal, Karoly
AU  - Mate, Zoltan
AU  - Katarova, Zoya
AU  - Szabo, Gabor
PY  - 2010
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/420
AB  - Gamma-amminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system of vertebrates, serves as an autocrine/paracrine signaling molecule during development, modulating a number of calcium (Ca2+)-dependent processes, including proliferation, migration, and differentiation, acting via 2 types of GABA receptors (GABARs): ionotropic GABA(A)Rs and metabotropic GABA(B)Rs. Here, we demonstrate that mouse embryonic stem cells (mESCs), which possess the capacity for virtually unlimited self-renewal and pluripotency, synthesize GABA and express functional GABA(A)Rs and GABA(B)Rs, as well as voltage-gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inwardly rectifying potassium (GIRK) channels. On activation, both GABAR types triggered synergistically intracellular calcium rise. Muscimol (a GABA(A)R agonist) induced single Ca2+ transients involving both VGCC-mediated Ca2+ influx and intracellular stores, while baclofen (a GABA(B)R agonist) evoked Ca2+ transients followed by intercellular Ca2+ waves and oscillations that were resistant to antagonists and entirely dependent on Ca2+ release from intracellular stores. Prolonged treatment with muscimol slightly inhibited, while baclofen or SR95531 (a GABA(A)R antagonist) significantly facilitated, mESC proliferation. GABA(A)R-specific ligands also induced morphological and gene expression changes indicating a differentiation shift. Our data suggest that the interplay between GABARs and downstream (coupled) effectors differentially modulates mESC proliferation/differentiation through selective activation of second messenger signaling cascades.-Schwirtlich, M., Emri, Z., Antal, K., Mate, Z., Katarova, Z., Szabo, G. GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+. FASEB J. 24, 1218-1228 (2010). www.fasebj.org
PB  - Federation Amer Soc Exp Biol, Bethesda
T2  - FASEB Journal
T1  - GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+
EP  - 1228
IS  - 4
SP  - 1218
VL  - 24
DO  - 10.1096/fj.09-143586
ER  - 
@article{
author = "Schwirtlich, Marija and Emri, Zsuzsa and Antal, Karoly and Mate, Zoltan and Katarova, Zoya and Szabo, Gabor",
year = "2010",
abstract = "Gamma-amminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system of vertebrates, serves as an autocrine/paracrine signaling molecule during development, modulating a number of calcium (Ca2+)-dependent processes, including proliferation, migration, and differentiation, acting via 2 types of GABA receptors (GABARs): ionotropic GABA(A)Rs and metabotropic GABA(B)Rs. Here, we demonstrate that mouse embryonic stem cells (mESCs), which possess the capacity for virtually unlimited self-renewal and pluripotency, synthesize GABA and express functional GABA(A)Rs and GABA(B)Rs, as well as voltage-gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inwardly rectifying potassium (GIRK) channels. On activation, both GABAR types triggered synergistically intracellular calcium rise. Muscimol (a GABA(A)R agonist) induced single Ca2+ transients involving both VGCC-mediated Ca2+ influx and intracellular stores, while baclofen (a GABA(B)R agonist) evoked Ca2+ transients followed by intercellular Ca2+ waves and oscillations that were resistant to antagonists and entirely dependent on Ca2+ release from intracellular stores. Prolonged treatment with muscimol slightly inhibited, while baclofen or SR95531 (a GABA(A)R antagonist) significantly facilitated, mESC proliferation. GABA(A)R-specific ligands also induced morphological and gene expression changes indicating a differentiation shift. Our data suggest that the interplay between GABARs and downstream (coupled) effectors differentially modulates mESC proliferation/differentiation through selective activation of second messenger signaling cascades.-Schwirtlich, M., Emri, Z., Antal, K., Mate, Z., Katarova, Z., Szabo, G. GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+. FASEB J. 24, 1218-1228 (2010). www.fasebj.org",
publisher = "Federation Amer Soc Exp Biol, Bethesda",
journal = "FASEB Journal",
title = "GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+",
pages = "1228-1218",
number = "4",
volume = "24",
doi = "10.1096/fj.09-143586"
}
Schwirtlich, M., Emri, Z., Antal, K., Mate, Z., Katarova, Z.,& Szabo, G.. (2010). GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+. in FASEB Journal
Federation Amer Soc Exp Biol, Bethesda., 24(4), 1218-1228.
https://doi.org/10.1096/fj.09-143586
Schwirtlich M, Emri Z, Antal K, Mate Z, Katarova Z, Szabo G. GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+. in FASEB Journal. 2010;24(4):1218-1228.
doi:10.1096/fj.09-143586 .
Schwirtlich, Marija, Emri, Zsuzsa, Antal, Karoly, Mate, Zoltan, Katarova, Zoya, Szabo, Gabor, "GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+" in FASEB Journal, 24, no. 4 (2010):1218-1228,
https://doi.org/10.1096/fj.09-143586 . .
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