TY  - JOUR
AU  - Balint, Vanda
AU  - Perić, Mina
AU  - Dačić, Sanja
AU  - Stanisavljević Ninković, Danijela
AU  - Marjanović, Jelena
AU  - Popović, Jelena
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
PY  - 2024
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2340
AB  - Astrocytes are the main homeostatic cells in the central nervous system, with the unique ability to transform from quiescent into a reactive state in response to pathological conditions by reacquiring some precursor properties. This process is known as reactive astrogliosis, a compensatory response that mediates tissue damage and recovery. Although it is well known that SOX transcription factors drive the expression of phenotype-specific genetic programs during neurodevelopment, their roles in mature astrocytes have not been studied extensively. We focused on the transcription factors SOX2 and SOX9, shown to be re-expressed in reactive astrocytes, in order to study the reactivation-related functional properties of astrocytes mediated by those proteins. We performed an initial screening of SOX2 and SOX9 expression after sensorimotor cortex ablation injury in rats and conducted gain-of-function studies in vitro using astrocytes derived from the human NT2/D1 cell line. Our results revealed the direct involvement of SOX2 in the reacquisition of proliferation in mature NT2/D1-derived astrocytes, while SOX9 overexpression increased migratory potential and glutamate uptake in these cells. Our results imply that modulation of SOX gene expression may change the functional properties of astrocytes, which holds promise for the discovery of potential therapeutic targets in the development of novel strategies for tissue regeneration and recovery.
PB  - MDPI
T2  - Biomedicines
T1  - The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes
IS  - 4
SP  - 796
VL  - 12
DO  - 10.3390/biomedicines12040796
ER  - 

@article{
author = "Balint, Vanda and Perić, Mina and Dačić, Sanja and Stanisavljević Ninković, Danijela and Marjanović, Jelena and Popović, Jelena and Stevanović, Milena and Lazić, Andrijana",
year = "2024",
abstract = "Astrocytes are the main homeostatic cells in the central nervous system, with the unique ability to transform from quiescent into a reactive state in response to pathological conditions by reacquiring some precursor properties. This process is known as reactive astrogliosis, a compensatory response that mediates tissue damage and recovery. Although it is well known that SOX transcription factors drive the expression of phenotype-specific genetic programs during neurodevelopment, their roles in mature astrocytes have not been studied extensively. We focused on the transcription factors SOX2 and SOX9, shown to be re-expressed in reactive astrocytes, in order to study the reactivation-related functional properties of astrocytes mediated by those proteins. We performed an initial screening of SOX2 and SOX9 expression after sensorimotor cortex ablation injury in rats and conducted gain-of-function studies in vitro using astrocytes derived from the human NT2/D1 cell line. Our results revealed the direct involvement of SOX2 in the reacquisition of proliferation in mature NT2/D1-derived astrocytes, while SOX9 overexpression increased migratory potential and glutamate uptake in these cells. Our results imply that modulation of SOX gene expression may change the functional properties of astrocytes, which holds promise for the discovery of potential therapeutic targets in the development of novel strategies for tissue regeneration and recovery.",
publisher = "MDPI",
journal = "Biomedicines",
title = "The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes",
number = "4",
pages = "796",
volume = "12",
doi = "10.3390/biomedicines12040796"
}

Balint, V., Perić, M., Dačić, S., Stanisavljević Ninković, D., Marjanović, J., Popović, J., Stevanović, M.,& Lazić, A.. (2024). The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes. in Biomedicines
MDPI., 12(4), 796.
https://doi.org/10.3390/biomedicines12040796

Balint V, Perić M, Dačić S, Stanisavljević Ninković D, Marjanović J, Popović J, Stevanović M, Lazić A. The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes. in Biomedicines. 2024;12(4):796.
doi:10.3390/biomedicines12040796 .

Balint, Vanda, Perić, Mina, Dačić, Sanja, Stanisavljević Ninković, Danijela, Marjanović, Jelena, Popović, Jelena, Stevanović, Milena, Lazić, Andrijana, "The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes" in Biomedicines, 12, no. 4 (2024):796,
https://doi.org/10.3390/biomedicines12040796 . .

TY  - CONF
AU  - Drakulić, Danijela
AU  - Petrakis, Spyros
AU  - Harwood, Adrian J.
AU  - Linden, David
AU  - Lazić, Andrijana
AU  - Kovačević-Grujičić, Nataša
AU  - Stevanović, Milena
PY  - 2024
UR  - https://www.ache-pub.org.rs/index.php/HemInd/article/view/1325
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2361
AB  - Neurodevelopmental disorders (NDDs) are caused by alterations in early brain development. They are a group of geographically dispersed, complex and heterogeneous disorders that give rise to the psychiatric conditions such as autism spectrum disorders, intellectual disability, schizophrenia and bipolar disorder. In order to build global research activity for study of NDDs, the main goals of the Twinning project STREAMLINE are to enhanced strategic networking and reinforce research and innovation potential of the Institute of Molecular Genetics and Genetic Engineering, University of Belgrade (IMGGE) in order to develop IMGGE as a high capacity hub for research of NDDs in the Western Balkans. This will be achieved by twinning IMGGE with three top-class research institutions in Europe (Cardiff University, University of Maastricht and Centre for Research and Technology Hellas) with an exceptional expertise in the stem cells based research of NDDs, -OMICS technologies, bioinformatics data analysis and drug testing and through staff exchanges, training, and organization of summer schools, Industry Open Days, symposia and workshops.
C3  - Hemijska industrija (Chemical Industry)
T1  - STREAMLINE HUB: a high capacity hub for research of neurodevelopmental disorders in the Western Balkan region
EP  - 78
IS  - 1S
SP  - 78
VL  - 78
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2361
ER  - 

@conference{
author = "Drakulić, Danijela and Petrakis, Spyros and Harwood, Adrian J. and Linden, David and Lazić, Andrijana and Kovačević-Grujičić, Nataša and Stevanović, Milena",
year = "2024",
abstract = "Neurodevelopmental disorders (NDDs) are caused by alterations in early brain development. They are a group of geographically dispersed, complex and heterogeneous disorders that give rise to the psychiatric conditions such as autism spectrum disorders, intellectual disability, schizophrenia and bipolar disorder. In order to build global research activity for study of NDDs, the main goals of the Twinning project STREAMLINE are to enhanced strategic networking and reinforce research and innovation potential of the Institute of Molecular Genetics and Genetic Engineering, University of Belgrade (IMGGE) in order to develop IMGGE as a high capacity hub for research of NDDs in the Western Balkans. This will be achieved by twinning IMGGE with three top-class research institutions in Europe (Cardiff University, University of Maastricht and Centre for Research and Technology Hellas) with an exceptional expertise in the stem cells based research of NDDs, -OMICS technologies, bioinformatics data analysis and drug testing and through staff exchanges, training, and organization of summer schools, Industry Open Days, symposia and workshops.",
journal = "Hemijska industrija (Chemical Industry)",
title = "STREAMLINE HUB: a high capacity hub for research of neurodevelopmental disorders in the Western Balkan region",
pages = "78-78",
number = "1S",
volume = "78",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2361"
}

Drakulić, D., Petrakis, S., Harwood, A. J., Linden, D., Lazić, A., Kovačević-Grujičić, N.,& Stevanović, M.. (2024). STREAMLINE HUB: a high capacity hub for research of neurodevelopmental disorders in the Western Balkan region. in Hemijska industrija (Chemical Industry), 78(1S), 78-78.
https://hdl.handle.net/21.15107/rcub_imagine_2361

Drakulić D, Petrakis S, Harwood AJ, Linden D, Lazić A, Kovačević-Grujičić N, Stevanović M. STREAMLINE HUB: a high capacity hub for research of neurodevelopmental disorders in the Western Balkan region. in Hemijska industrija (Chemical Industry). 2024;78(1S):78-78.
https://hdl.handle.net/21.15107/rcub_imagine_2361 .

Drakulić, Danijela, Petrakis, Spyros, Harwood, Adrian J., Linden, David, Lazić, Andrijana, Kovačević-Grujičić, Nataša, Stevanović, Milena, "STREAMLINE HUB: a high capacity hub for research of neurodevelopmental disorders in the Western Balkan region" in Hemijska industrija (Chemical Industry), 78, no. 1S (2024):78-78,
https://hdl.handle.net/21.15107/rcub_imagine_2361 .

TY  - CONF
AU  - Balint, Vanda
AU  - Stanisavljević-Ninković, Danijela
AU  - Lazić, Stefan
AU  - Kovačević-Grujičić, Nataša
AU  - Perić, Mina
AU  - Pejić, Jelena
AU  - Mojsin, Marija
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2185
AB  - Astrocytes are the main homeostatic cells in the brain with important roles both in
physiological and pathological conditions. They have a unique ability to become
reactivated in response to different types of brain pathologies, which serves as a
compensatory response that modulates tissue damage and recovery. Also, senescent
astrocytes have profound implications in age-related neurodegenerative disorders. The
molecular mechanisms underlying astrocyte reactivation and senescence are still not
well understood. To investigate the roles of SOX2 and SOX9 transcription factors and
miR-21 in these phenotypic alternations of astroglia, astrocytes derived from NT2/D1
cell line (NT2/A) were used as a model system. Western blot analyses showed that the
expression of both SOX2 and SOX9 decreases during the maturation of NT2/A and
they are re-expressed upon in vitro induced injury. Further modulation of the SOX2
and SOX9 expression will reveal their roles in the regulation of astrocytes
reactivation. Down-regulation of mir-21 in both immature and mature NT2/A by
using the antisense technology, induced the decline in cell proliferation revealed by
Ki67 proliferation marker. Also the premature cellular senescence was induced as
indicated by increase in SA-ß-gal activity and the expression of p21 and p53.
Additionally, in silico analysis predicted many of the genes, previously shown to be
upregulated in senescent astrocytes, as miR-21 targets.
Clarifying the roles of SOX genes and miRNAs in astrocyte reactivation and
senescence would contribute to better understanding of the functions of these cells at
the molecular level, which holds promise for development of new therapeutic
strategies.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of the Serbian Neuroscience Society
T1  - The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells
EP  - 99
SP  - 99
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2185
ER  - 

@conference{
author = "Balint, Vanda and Stanisavljević-Ninković, Danijela and Lazić, Stefan and Kovačević-Grujičić, Nataša and Perić, Mina and Pejić, Jelena and Mojsin, Marija and Stevanović, Milena and Lazić, Andrijana",
year = "2023",
abstract = "Astrocytes are the main homeostatic cells in the brain with important roles both in
physiological and pathological conditions. They have a unique ability to become
reactivated in response to different types of brain pathologies, which serves as a
compensatory response that modulates tissue damage and recovery. Also, senescent
astrocytes have profound implications in age-related neurodegenerative disorders. The
molecular mechanisms underlying astrocyte reactivation and senescence are still not
well understood. To investigate the roles of SOX2 and SOX9 transcription factors and
miR-21 in these phenotypic alternations of astroglia, astrocytes derived from NT2/D1
cell line (NT2/A) were used as a model system. Western blot analyses showed that the
expression of both SOX2 and SOX9 decreases during the maturation of NT2/A and
they are re-expressed upon in vitro induced injury. Further modulation of the SOX2
and SOX9 expression will reveal their roles in the regulation of astrocytes
reactivation. Down-regulation of mir-21 in both immature and mature NT2/A by
using the antisense technology, induced the decline in cell proliferation revealed by
Ki67 proliferation marker. Also the premature cellular senescence was induced as
indicated by increase in SA-ß-gal activity and the expression of p21 and p53.
Additionally, in silico analysis predicted many of the genes, previously shown to be
upregulated in senescent astrocytes, as miR-21 targets.
Clarifying the roles of SOX genes and miRNAs in astrocyte reactivation and
senescence would contribute to better understanding of the functions of these cells at
the molecular level, which holds promise for development of new therapeutic
strategies.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of the Serbian Neuroscience Society",
title = "The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells",
pages = "99-99",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2185"
}

Balint, V., Stanisavljević-Ninković, D., Lazić, S., Kovačević-Grujičić, N., Perić, M., Pejić, J., Mojsin, M., Stevanović, M.,& Lazić, A.. (2023). The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells. in 8th Congress of the Serbian Neuroscience Society
Belgrade : Serbian Neuroscience Society., 99-99.
https://hdl.handle.net/21.15107/rcub_imagine_2185

Balint V, Stanisavljević-Ninković D, Lazić S, Kovačević-Grujičić N, Perić M, Pejić J, Mojsin M, Stevanović M, Lazić A. The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells. in 8th Congress of the Serbian Neuroscience Society. 2023;:99-99.
https://hdl.handle.net/21.15107/rcub_imagine_2185 .

Balint, Vanda, Stanisavljević-Ninković, Danijela, Lazić, Stefan, Kovačević-Grujičić, Nataša, Perić, Mina, Pejić, Jelena, Mojsin, Marija, Stevanović, Milena, Lazić, Andrijana, "The role of specific SOX genes and microRNAs in reactivation and senescence of human astrocytes derived from pluripotent NT2/D1 cells" in 8th Congress of the Serbian Neuroscience Society (2023):99-99,
https://hdl.handle.net/21.15107/rcub_imagine_2185 .

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 . .

TY  - CONF
AU  - Balint, Vanda
AU  - Stanisavljević Ninković, Danijela
AU  - Anastasov, Nataša
AU  - Lazić, Stefan
AU  - Kovačević-Grujičić, Nataša
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
AU  - Krstić, Aleksandra
AU  - Pejić, Jelena
PY  - 2022
UR  - https://doi.org/10.21175/rad.spr.abstr.book.2022.22.1
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1864
AB  - Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical,
metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of
senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular
mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have
shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms.
Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link
between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21
in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1
cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense
technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence
hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescenceassociated
β-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously
shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken
together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our
knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes.
Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic
strategies based on miRNA manipulation could prevent senescence and may improve the physiological
outcome.
C3  - RAD International concerence on radiation in various fields of research
T1  - Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes
IS  - Spring Edition
SP  - 90
DO  - 10.21175/rad.spr.abstr.book.2022.22.1
ER  - 

@conference{
author = "Balint, Vanda and Stanisavljević Ninković, Danijela and Anastasov, Nataša and Lazić, Stefan and Kovačević-Grujičić, Nataša and Stevanović, Milena and Lazić, Andrijana and Krstić, Aleksandra and Pejić, Jelena",
year = "2022",
abstract = "Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical,
metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of
senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular
mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have
shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms.
Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link
between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21
in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1
cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense
technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence
hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescenceassociated
β-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously
shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken
together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our
knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes.
Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic
strategies based on miRNA manipulation could prevent senescence and may improve the physiological
outcome.",
journal = "RAD International concerence on radiation in various fields of research",
title = "Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes",
number = "Spring Edition",
pages = "90",
doi = "10.21175/rad.spr.abstr.book.2022.22.1"
}

Balint, V., Stanisavljević Ninković, D., Anastasov, N., Lazić, S., Kovačević-Grujičić, N., Stevanović, M., Lazić, A., Krstić, A.,& Pejić, J.. (2022). Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes. in RAD International concerence on radiation in various fields of research(Spring Edition), 90.
https://doi.org/10.21175/rad.spr.abstr.book.2022.22.1

Balint V, Stanisavljević Ninković D, Anastasov N, Lazić S, Kovačević-Grujičić N, Stevanović M, Lazić A, Krstić A, Pejić J. Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes. in RAD International concerence on radiation in various fields of research. 2022;(Spring Edition):90.
doi:10.21175/rad.spr.abstr.book.2022.22.1 .

Balint, Vanda, Stanisavljević Ninković, Danijela, Anastasov, Nataša, Lazić, Stefan, Kovačević-Grujičić, Nataša, Stevanović, Milena, Lazić, Andrijana, Krstić, Aleksandra, Pejić, Jelena, "Inhibition of miR-21 promotes cellular senescence in NT2-derived astrocytes" in RAD International concerence on radiation in various fields of research, no. Spring Edition (2022):90,
https://doi.org/10.21175/rad.spr.abstr.book.2022.22.1 . .

TY  - JOUR
AU  - Lazić, Andrijana
AU  - Balint, Vanda
AU  - Stanisavljević Ninković, Danijela
AU  - Perić, Mina
AU  - Stevanović, Milena
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1602
AB  - Astrocytes, as the most abundant glial cells in the central nervous system, are tightly integrated into neural networks and participate in numerous aspects of brain physiology and pathology. They are the main homeostatic cells in the central nervous system, and the loss of astrocyte physiological functions and/or gain of pro-inflammatory functions, due to their reactivation or cellular senescence, can have profound impacts on the surrounding microenvironment with pathological outcomes. Although the importance of astrocytes is generally recognized, and both senescence and reactive astrogliosis have been extensively reviewed independently, there are only a few comparative overviews of these complex processes. In this review, we summarize the latest data regarding astrocyte reactivation and senescence, and outline similarities and differences between these phenotypes from morphological, functional, and molecular points of view. A special focus has been given to neurodegenerative diseases, where these phenotypic alternations of astrocytes are significantly implicated. We also summarize current perspectives regarding new advances in model systems based on astrocytes as well as data pointing to these glial cells as potential therapeutic targets.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies
IS  - 9
VL  - 23
DO  - 10.3390/ijms23094995
ER  - 

@article{
author = "Lazić, Andrijana and Balint, Vanda and Stanisavljević Ninković, Danijela and Perić, Mina and Stevanović, Milena",
year = "2022",
abstract = "Astrocytes, as the most abundant glial cells in the central nervous system, are tightly integrated into neural networks and participate in numerous aspects of brain physiology and pathology. They are the main homeostatic cells in the central nervous system, and the loss of astrocyte physiological functions and/or gain of pro-inflammatory functions, due to their reactivation or cellular senescence, can have profound impacts on the surrounding microenvironment with pathological outcomes. Although the importance of astrocytes is generally recognized, and both senescence and reactive astrogliosis have been extensively reviewed independently, there are only a few comparative overviews of these complex processes. In this review, we summarize the latest data regarding astrocyte reactivation and senescence, and outline similarities and differences between these phenotypes from morphological, functional, and molecular points of view. A special focus has been given to neurodegenerative diseases, where these phenotypic alternations of astrocytes are significantly implicated. We also summarize current perspectives regarding new advances in model systems based on astrocytes as well as data pointing to these glial cells as potential therapeutic targets.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies",
number = "9",
volume = "23",
doi = "10.3390/ijms23094995"
}

Lazić, A., Balint, V., Stanisavljević Ninković, D., Perić, M.,& Stevanović, M.. (2022). Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies. in International Journal of Molecular Sciences
MDPI, Basel., 23(9).
https://doi.org/10.3390/ijms23094995

Lazić A, Balint V, Stanisavljević Ninković D, Perić M, Stevanović M. Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies. in International Journal of Molecular Sciences. 2022;23(9).
doi:10.3390/ijms23094995 .

Lazić, Andrijana, Balint, Vanda, Stanisavljević Ninković, Danijela, Perić, Mina, Stevanović, Milena, "Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies" in International Journal of Molecular Sciences, 23, no. 9 (2022),
https://doi.org/10.3390/ijms23094995 . .

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 . .

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 . .

TY  - JOUR
AU  - Balint, Vanda
AU  - Stanisavljević Ninković, Danijela
AU  - Anastasov, Nataša
AU  - Lazić, Stefan
AU  - Kovačević Grujičić, Nataša
AU  - Stevanović, Milena
AU  - Lazić, Andrijana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1472
AB  - Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical, metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms. Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21 in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1 cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescence-associated beta-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes. Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic strategies based on miRNA manipulation could prevent senescence and may improve the physiological outcome.
PB  - Maik Nauka/Interperiodica/Springer, New York
T2  - Biochemistry-Moscow
T1  - Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes
EP  - 1445
IS  - 11
SP  - 1434
VL  - 86
DO  - 10.1134/S0006297921110079
ER  - 

@article{
author = "Balint, Vanda and Stanisavljević Ninković, Danijela and Anastasov, Nataša and Lazić, Stefan and Kovačević Grujičić, Nataša and Stevanović, Milena and Lazić, Andrijana",
year = "2021",
abstract = "Astrocytes are the main homeostatic cells in the central nervous system (CNS) that provide mechanical, metabolic, and trophic support to neurons. Disruption of their physiological role or acquisition of senescence-associated phenotype can contribute to the CNS dysfunction and pathology. However, molecular mechanisms underlying the complex physiology of astrocytes are explored insufficiently. Recent studies have shown that miRNAs are involved in the regulation of astrocyte function through different mechanisms. Although miR-21 has been reported as an astrocytic miRNA with an important role in astrogliosis, no link between this miRNA and cellular senescence of astrocytes has been identified. To address the role of miR-21 in astrocytes, with special focus on cellular senescence, we used NT2/A (astrocytes derived from NT2/D1 cells). Downregulation of miR-21 expression in both immature and mature NT2/A by the antisense technology induced the arrest of cell growth and premature cellular senescence, as indicated by senescence hallmarks such as increased expression of cell cycle inhibitors p21 and p53 and augmented senescence-associated beta-galactosidase activity. Additionally, in silico analysis predicted many of the genes, previously shown to be upregulated in astrocytes with the irradiation-induced senescence, as miR-21 targets. Taken together, our results point to miR-21 as a potential regulator of astrocyte senescence. To the best of our knowledge, these are the first data showing the link between miR-21 and cellular senescence of astrocytes. Since senescent astrocytes are associated with different CNS pathologies, development of novel therapeutic strategies based on miRNA manipulation could prevent senescence and may improve the physiological outcome.",
publisher = "Maik Nauka/Interperiodica/Springer, New York",
journal = "Biochemistry-Moscow",
title = "Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes",
pages = "1445-1434",
number = "11",
volume = "86",
doi = "10.1134/S0006297921110079"
}

Balint, V., Stanisavljević Ninković, D., Anastasov, N., Lazić, S., Kovačević Grujičić, N., Stevanović, M.,& Lazić, A.. (2021). Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes. in Biochemistry-Moscow
Maik Nauka/Interperiodica/Springer, New York., 86(11), 1434-1445.
https://doi.org/10.1134/S0006297921110079

Balint V, Stanisavljević Ninković D, Anastasov N, Lazić S, Kovačević Grujičić N, Stevanović M, Lazić A. Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes. in Biochemistry-Moscow. 2021;86(11):1434-1445.
doi:10.1134/S0006297921110079 .

Balint, Vanda, Stanisavljević Ninković, Danijela, Anastasov, Nataša, Lazić, Stefan, Kovačević Grujičić, Nataša, Stevanović, Milena, Lazić, Andrijana, "Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes" in Biochemistry-Moscow, 86, no. 11 (2021):1434-1445,
https://doi.org/10.1134/S0006297921110079 . .

TY  - JOUR
AU  - Lazić, Andrijana
AU  - Popović, Jelena
AU  - Paunesku, Tatjana
AU  - Woloschak, Gayle E.
AU  - Stevanović, Milena
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1385
AB  - Cancer is a global health problem that is often successfully addressed by therapy, with cancer survivors increasing in numbers and living longer world around. Although new cancer treatment options are continuously explored, platinum based chemotherapy agents remain in use due to their efficiency and availability. Unfortunately, all cancer therapies affect normal tissues as well as cancer, and more than 40 specific side effects of platinum based drugs documented so far decrease the quality of life of cancer survivors. Chemotherapy-induced peripheral neuropathy is a frequent side effects of platinum-based chemotherapy agents. This cluster of complications is often so debilitating that patients occasionally have to discontinue the therapy. Sensory neurons of dorsal root ganglia are at the core of chemotherapy-induced peripheral neuropathy symptoms. In these postmitotic cells, DNA damage caused by platinum chemotherapy interferes with normal functioning. Accumulation of DNA-platinum adducts correlates with neurotoxic severity and development of sensation of pain. While biochemistry of DNA-platinum adducts is the same in all cell types, molecular mechanisms affected by DNA-platinum adducts are different in cancer cells and non-dividing cells. This review aims to raise awareness about platinum associated chemotherapy-induced peripheral neuropathy as a medical problem that has remained unexplained for decades. We emphasize the complexity of this condition both from clinical and mechanistical point of view and focus on recent findings about chemotherapy-induced peripheral neuropathy in in vitro and in vivo model systems. Finally, we summarize current perspectives about clinical approaches for chemotherapy-induced peripheral neuropathy treatment.
PB  - Wolters Kluwer Medknow Publications, Mumbai
T2  - Neural Regeneration Research
T1  - Insights into platinum-induced peripheral neuropathy-current perspective
EP  - 1630
IS  - 9
SP  - 1623
VL  - 15
DO  - 10.4103/1673-5374.276321
ER  - 

@article{
author = "Lazić, Andrijana and Popović, Jelena and Paunesku, Tatjana and Woloschak, Gayle E. and Stevanović, Milena",
year = "2020",
abstract = "Cancer is a global health problem that is often successfully addressed by therapy, with cancer survivors increasing in numbers and living longer world around. Although new cancer treatment options are continuously explored, platinum based chemotherapy agents remain in use due to their efficiency and availability. Unfortunately, all cancer therapies affect normal tissues as well as cancer, and more than 40 specific side effects of platinum based drugs documented so far decrease the quality of life of cancer survivors. Chemotherapy-induced peripheral neuropathy is a frequent side effects of platinum-based chemotherapy agents. This cluster of complications is often so debilitating that patients occasionally have to discontinue the therapy. Sensory neurons of dorsal root ganglia are at the core of chemotherapy-induced peripheral neuropathy symptoms. In these postmitotic cells, DNA damage caused by platinum chemotherapy interferes with normal functioning. Accumulation of DNA-platinum adducts correlates with neurotoxic severity and development of sensation of pain. While biochemistry of DNA-platinum adducts is the same in all cell types, molecular mechanisms affected by DNA-platinum adducts are different in cancer cells and non-dividing cells. This review aims to raise awareness about platinum associated chemotherapy-induced peripheral neuropathy as a medical problem that has remained unexplained for decades. We emphasize the complexity of this condition both from clinical and mechanistical point of view and focus on recent findings about chemotherapy-induced peripheral neuropathy in in vitro and in vivo model systems. Finally, we summarize current perspectives about clinical approaches for chemotherapy-induced peripheral neuropathy treatment.",
publisher = "Wolters Kluwer Medknow Publications, Mumbai",
journal = "Neural Regeneration Research",
title = "Insights into platinum-induced peripheral neuropathy-current perspective",
pages = "1630-1623",
number = "9",
volume = "15",
doi = "10.4103/1673-5374.276321"
}

Lazić, A., Popović, J., Paunesku, T., Woloschak, G. E.,& Stevanović, M.. (2020). Insights into platinum-induced peripheral neuropathy-current perspective. in Neural Regeneration Research
Wolters Kluwer Medknow Publications, Mumbai., 15(9), 1623-1630.
https://doi.org/10.4103/1673-5374.276321

Lazić A, Popović J, Paunesku T, Woloschak GE, Stevanović M. Insights into platinum-induced peripheral neuropathy-current perspective. in Neural Regeneration Research. 2020;15(9):1623-1630.
doi:10.4103/1673-5374.276321 .

Lazić, Andrijana, Popović, Jelena, Paunesku, Tatjana, Woloschak, Gayle E., Stevanović, Milena, "Insights into platinum-induced peripheral neuropathy-current perspective" in Neural Regeneration Research, 15, no. 9 (2020):1623-1630,
https://doi.org/10.4103/1673-5374.276321 . .

TY  - JOUR
AU  - Popović, Jelena
AU  - Lazić, Andrijana
AU  - Paunesku, Tatjana
AU  - Ma, Qing
AU  - Chen, Si
AU  - Lai, Barry
AU  - Stevanović, Milena
AU  - Woloschak, Gayle E.
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1255
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin. In addition, WR1065 protects the non-dividing neurons by decreasing cisplatin caused oxidative stress and apoptosis. Accumulation of Pt in cisplatin-treated cells was heterogeneous, but the frequency and concentration of Pt in cells were lowered in the presence of WR1065 as shown by X-ray fluorescence microscopy (XFM). Transition metals accumulation accompanied Pt increase in cells; this effect was equally diminished in the presence of WR1065. To analyze possible chemical modulation of Pt-DNA bonds, we examined the platinum L-III near edge spectrum by X-ray absorption spectroscopy. The spectrum found in cisplatin-DNA samples is altered differently by the addition of either WR1065 or sodium azide. Importantly, a similar change in Pt edge spectra was noted in cells treated with cisplatin and WR1065. Therefore, amifostine should be reconsidered as a candidate for treatments that reduce or prevent CIPN.
PB  - Springer/Plenum Publishers, New York
T2  - Cellular and Molecular Neurobiology
T1  - Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro
EP  - 636
IS  - 5
SP  - 619
VL  - 39
DO  - 10.1007/s10571-019-00667-7
ER  - 

@article{
author = "Popović, Jelena and Lazić, Andrijana and Paunesku, Tatjana and Ma, Qing and Chen, Si and Lai, Barry and Stevanović, Milena and Woloschak, Gayle E.",
year = "2019",
abstract = "Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin. In addition, WR1065 protects the non-dividing neurons by decreasing cisplatin caused oxidative stress and apoptosis. Accumulation of Pt in cisplatin-treated cells was heterogeneous, but the frequency and concentration of Pt in cells were lowered in the presence of WR1065 as shown by X-ray fluorescence microscopy (XFM). Transition metals accumulation accompanied Pt increase in cells; this effect was equally diminished in the presence of WR1065. To analyze possible chemical modulation of Pt-DNA bonds, we examined the platinum L-III near edge spectrum by X-ray absorption spectroscopy. The spectrum found in cisplatin-DNA samples is altered differently by the addition of either WR1065 or sodium azide. Importantly, a similar change in Pt edge spectra was noted in cells treated with cisplatin and WR1065. Therefore, amifostine should be reconsidered as a candidate for treatments that reduce or prevent CIPN.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Cellular and Molecular Neurobiology",
title = "Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro",
pages = "636-619",
number = "5",
volume = "39",
doi = "10.1007/s10571-019-00667-7"
}

Popović, J., Lazić, A., Paunesku, T., Ma, Q., Chen, S., Lai, B., Stevanović, M.,& Woloschak, G. E.. (2019). Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro. in Cellular and Molecular Neurobiology
Springer/Plenum Publishers, New York., 39(5), 619-636.
https://doi.org/10.1007/s10571-019-00667-7

Popović J, Lazić A, Paunesku T, Ma Q, Chen S, Lai B, Stevanović M, Woloschak GE. Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro. in Cellular and Molecular Neurobiology. 2019;39(5):619-636.
doi:10.1007/s10571-019-00667-7 .

Popović, Jelena, Lazić, Andrijana, Paunesku, Tatjana, Ma, Qing, Chen, Si, Lai, Barry, Stevanović, Milena, Woloschak, Gayle E., "Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro" in Cellular and Molecular Neurobiology, 39, no. 5 (2019):619-636,
https://doi.org/10.1007/s10571-019-00667-7 . .

TY  - CONF
AU  - Paunesku, Tatjana
AU  - Popović, Jelena
AU  - Klajn, Andrijana
AU  - Kovačević Grujičić, Nataša
AU  - Ma, Qing
AU  - Stevanović, Milena
AU  - Woloschak, Gayle E.
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1167
PB  - Amer Assoc Cancer Research, Philadelphia
C3  - Cancer Research
T1  - WR1065, the active metabolite of amifostine modulates chemistry and biology of cisplatin
IS  - 13
VL  - 78
DO  - 10.1158/1538-7445.AM2018-456
ER  - 

@conference{
author = "Paunesku, Tatjana and Popović, Jelena and Klajn, Andrijana and Kovačević Grujičić, Nataša and Ma, Qing and Stevanović, Milena and Woloschak, Gayle E.",
year = "2018",
publisher = "Amer Assoc Cancer Research, Philadelphia",
journal = "Cancer Research",
title = "WR1065, the active metabolite of amifostine modulates chemistry and biology of cisplatin",
number = "13",
volume = "78",
doi = "10.1158/1538-7445.AM2018-456"
}

Paunesku, T., Popović, J., Klajn, A., Kovačević Grujičić, N., Ma, Q., Stevanović, M.,& Woloschak, G. E.. (2018). WR1065, the active metabolite of amifostine modulates chemistry and biology of cisplatin. in Cancer Research
Amer Assoc Cancer Research, Philadelphia., 78(13).
https://doi.org/10.1158/1538-7445.AM2018-456

Paunesku T, Popović J, Klajn A, Kovačević Grujičić N, Ma Q, Stevanović M, Woloschak GE. WR1065, the active metabolite of amifostine modulates chemistry and biology of cisplatin. in Cancer Research. 2018;78(13).
doi:10.1158/1538-7445.AM2018-456 .

Paunesku, Tatjana, Popović, Jelena, Klajn, Andrijana, Kovačević Grujičić, Nataša, Ma, Qing, Stevanović, Milena, Woloschak, Gayle E., "WR1065, the active metabolite of amifostine modulates chemistry and biology of cisplatin" in Cancer Research, 78, no. 13 (2018),
https://doi.org/10.1158/1538-7445.AM2018-456 . .

TY  - JOUR
AU  - Jasnić, Jovana
AU  - Lazić, Andrijana
AU  - Milivojević, Milena
AU  - Mojsin, Marija
AU  - Nikčević, Gordana
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/807
AB  - Serum is generally regarded as an essential component of many eukaryotic cell culture media, despite the fact that serum composition varies greatly and may be the source of a wide range of artefacts. The objective of this study was to assess serum-free growth conditions for the human embryonal carcinoma cell line, NT2/D1. These cells greatly resemble embryonic stem cells. In the presence of retinoic acid (RA), NT2/D1 cells irreversibly differentiate along the neuronal lineage. We have previously shown that the early phases of neural induction of these cells by RA involve the up-regulation of SOX3 gene expression. Our goal was to compare RA-induced differentiation of NT2/D1 cells in serum-containing and serum-free media, by using SOX3 protein levels as a marker of differentiation. We found that NT2/D1 cells can be successfully grown under serum-free conditions, and that the presence or absence of serum does not affect the level of SOX3 protein after a 48-hour RA induction. However, six days of RA treatment resulted in a marked increase in SOX3 protein levels in serum-free media compared to serum-containing media, indicating that serum might have an inhibitory effect on the expression of this neural differentiation marker. This finding is important for both basic and translational studies that hope to exploit cell culture conditions that are free of animal-derived products.
PB  - Sage Publications Ltd, London
T2  - ATLA-Alternatives To Laboratory Animals
T1  - Human Embryonal Carcinoma Cells in Serum-free Conditions as an In Vitro Model System of Neural Differentiation
EP  - 18
IS  - 1
SP  - 9
VL  - 43
DO  - 10.1177/026119291504300105
ER  - 

@article{
author = "Jasnić, Jovana and Lazić, Andrijana and Milivojević, Milena and Mojsin, Marija and Nikčević, Gordana",
year = "2015",
abstract = "Serum is generally regarded as an essential component of many eukaryotic cell culture media, despite the fact that serum composition varies greatly and may be the source of a wide range of artefacts. The objective of this study was to assess serum-free growth conditions for the human embryonal carcinoma cell line, NT2/D1. These cells greatly resemble embryonic stem cells. In the presence of retinoic acid (RA), NT2/D1 cells irreversibly differentiate along the neuronal lineage. We have previously shown that the early phases of neural induction of these cells by RA involve the up-regulation of SOX3 gene expression. Our goal was to compare RA-induced differentiation of NT2/D1 cells in serum-containing and serum-free media, by using SOX3 protein levels as a marker of differentiation. We found that NT2/D1 cells can be successfully grown under serum-free conditions, and that the presence or absence of serum does not affect the level of SOX3 protein after a 48-hour RA induction. However, six days of RA treatment resulted in a marked increase in SOX3 protein levels in serum-free media compared to serum-containing media, indicating that serum might have an inhibitory effect on the expression of this neural differentiation marker. This finding is important for both basic and translational studies that hope to exploit cell culture conditions that are free of animal-derived products.",
publisher = "Sage Publications Ltd, London",
journal = "ATLA-Alternatives To Laboratory Animals",
title = "Human Embryonal Carcinoma Cells in Serum-free Conditions as an In Vitro Model System of Neural Differentiation",
pages = "18-9",
number = "1",
volume = "43",
doi = "10.1177/026119291504300105"
}

Jasnić, J., Lazić, A., Milivojević, M., Mojsin, M.,& Nikčević, G.. (2015). Human Embryonal Carcinoma Cells in Serum-free Conditions as an In Vitro Model System of Neural Differentiation. in ATLA-Alternatives To Laboratory Animals
Sage Publications Ltd, London., 43(1), 9-18.
https://doi.org/10.1177/026119291504300105

Jasnić J, Lazić A, Milivojević M, Mojsin M, Nikčević G. Human Embryonal Carcinoma Cells in Serum-free Conditions as an In Vitro Model System of Neural Differentiation. in ATLA-Alternatives To Laboratory Animals. 2015;43(1):9-18.
doi:10.1177/026119291504300105 .

Jasnić, Jovana, Lazić, Andrijana, Milivojević, Milena, Mojsin, Marija, Nikčević, Gordana, "Human Embryonal Carcinoma Cells in Serum-free Conditions as an In Vitro Model System of Neural Differentiation" in ATLA-Alternatives To Laboratory Animals, 43, no. 1 (2015):9-18,
https://doi.org/10.1177/026119291504300105 . .

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 . .

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 . .

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 . .

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 . .

TY  - JOUR
AU  - Mikulak, Joanna
AU  - Negrini, Sara
AU  - Lazić, Andrijana
AU  - D'Alessandro, Rosalba
AU  - Mavilio, Domenico
AU  - Meldolesi, Jacopo
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/581
AB  - L1 cell adhesion molecule (L1CAM), an adhesion/signaling protein encoded by a gene target of the transcription repressor RE-1-Silencing Transcription factor (REST), is expressed in two alternatively spliced isoforms. The full-length isoform, typical of low-REST neural cells, plays key roles in survival/migration, outgrowth/fasciculation/regeneration of axons, synaptic plasticity; the isoform missing two mini-exons, abundant in a few high-REST non-neural cells, maintains some effect on migration and proliferation. To investigate whether and how L1CAM alternative splicing depends on REST we used neural cell models expressing low or high levels of REST (PC12, SH-SY5Y, differentiated NT2/D1 and primary neurons transduced or not with REST). The short isoform was found to rise when the low-REST levels of neural cells were experimentally increased, while the full-length isoform increased in high-REST cells when the repressor tone was attenuated. These results were due to Nova2, a neural cell-specific splicing factor shown here to be repressed by REST. REST control of L1CAM occurs therefore by two mechanisms, transcription and alternative splicing. The splicing mechanism, affecting not only L1CAM but all Nova2 targets (similar to 7% of brain-specific splicing, including the mRNAs of other adhesion and synaptic proteins) is expected to be critical during development and important also for the structure and function of mature neural cells.
PB  - Wiley, Hoboken
T2  - Journal of Neurochemistry
T1  - Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells
EP  - 709
IS  - 5
SP  - 699
VL  - 120
DO  - 10.1111/j.1471-4159.2011.07626.x
ER  - 

@article{
author = "Mikulak, Joanna and Negrini, Sara and Lazić, Andrijana and D'Alessandro, Rosalba and Mavilio, Domenico and Meldolesi, Jacopo",
year = "2012",
abstract = "L1 cell adhesion molecule (L1CAM), an adhesion/signaling protein encoded by a gene target of the transcription repressor RE-1-Silencing Transcription factor (REST), is expressed in two alternatively spliced isoforms. The full-length isoform, typical of low-REST neural cells, plays key roles in survival/migration, outgrowth/fasciculation/regeneration of axons, synaptic plasticity; the isoform missing two mini-exons, abundant in a few high-REST non-neural cells, maintains some effect on migration and proliferation. To investigate whether and how L1CAM alternative splicing depends on REST we used neural cell models expressing low or high levels of REST (PC12, SH-SY5Y, differentiated NT2/D1 and primary neurons transduced or not with REST). The short isoform was found to rise when the low-REST levels of neural cells were experimentally increased, while the full-length isoform increased in high-REST cells when the repressor tone was attenuated. These results were due to Nova2, a neural cell-specific splicing factor shown here to be repressed by REST. REST control of L1CAM occurs therefore by two mechanisms, transcription and alternative splicing. The splicing mechanism, affecting not only L1CAM but all Nova2 targets (similar to 7% of brain-specific splicing, including the mRNAs of other adhesion and synaptic proteins) is expected to be critical during development and important also for the structure and function of mature neural cells.",
publisher = "Wiley, Hoboken",
journal = "Journal of Neurochemistry",
title = "Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells",
pages = "709-699",
number = "5",
volume = "120",
doi = "10.1111/j.1471-4159.2011.07626.x"
}

Mikulak, J., Negrini, S., Lazić, A., D'Alessandro, R., Mavilio, D.,& Meldolesi, J.. (2012). Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells. in Journal of Neurochemistry
Wiley, Hoboken., 120(5), 699-709.
https://doi.org/10.1111/j.1471-4159.2011.07626.x

Mikulak J, Negrini S, Lazić A, D'Alessandro R, Mavilio D, Meldolesi J. Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells. in Journal of Neurochemistry. 2012;120(5):699-709.
doi:10.1111/j.1471-4159.2011.07626.x .

Mikulak, Joanna, Negrini, Sara, Lazić, Andrijana, D'Alessandro, Rosalba, Mavilio, Domenico, Meldolesi, Jacopo, "Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells" in Journal of Neurochemistry, 120, no. 5 (2012):699-709,
https://doi.org/10.1111/j.1471-4159.2011.07626.x . .

TY  - JOUR
AU  - Tomasoni, Romana
AU  - Negrini, Sara
AU  - Fiordaliso, Stefania
AU  - Lazić, Andrijana
AU  - Tkatch, Tatiana
AU  - Mondino, Anna
AU  - Meldolesi, Jacopo
AU  - D'Alessandro, Rosalba
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/480
AB  - The RE-1-specific silencing transcription factor (REST or NRSF) is a transcription repressor that orchestrates differentiation and also operates in differentiated neurons and neurosecretory cells (neural cells). Its role in proliferation has been investigated so far only in rapidly growing tumors, with conflicting results: suppression in non-neural tumors, stimulation in medulloblastomas. Working with two clones of chromaffin-neuronal PC12 cells, which express different levels of REST, and using genetic complementation and knockdown approaches, we show that REST also promotes proliferation in differentiated neural cells. Mechanistically, this occurs by a signaling pathway involving REST, the GTPase-activating protein tuberin (TSC2) and the transcription co-factor beta-catenin. In PC12 cells, raised expression of REST correlates with reduced TSC2 levels, nuclear accumulation and co-transcriptional activation of beta-catenin, and increased expression of its target oncogenes Myc and Ccnd1, which might account for the proliferation advantage and the distinct morphology. Rest transcription is also increased, unveiling the existence of a self-sustaining, feed-forward REST-TSC2-beta-catenin signaling loop that is also operative in another neural cell model, NT2/D1 cells. Transfection of REST, knockdown of TSC2 or forced expression of active beta-catenin recapitulated the biochemical, functional and morphological properties of the high-expressing REST clone in wild-type PC12 cells. Upregulation of REST promoted proliferation and phenotypic changes, thus hindering neurosecretion. The new REST-TSC2-beta-catenin signaling paradigm might have an important role in various aspects of neural cell physiology and pathology, including the regulation of proliferation and neurosecretion.
PB  - Company Biologists Ltd, Cambridge
T2  - Journal of Cell Science
T1  - A signaling loop of REST, TSC2 and beta-catenin governs proliferation and function of PC12 neural cells
EP  - 3186
IS  - 18
SP  - 3174
VL  - 124
DO  - 10.1242/jcs.087551
ER  - 

@article{
author = "Tomasoni, Romana and Negrini, Sara and Fiordaliso, Stefania and Lazić, Andrijana and Tkatch, Tatiana and Mondino, Anna and Meldolesi, Jacopo and D'Alessandro, Rosalba",
year = "2011",
abstract = "The RE-1-specific silencing transcription factor (REST or NRSF) is a transcription repressor that orchestrates differentiation and also operates in differentiated neurons and neurosecretory cells (neural cells). Its role in proliferation has been investigated so far only in rapidly growing tumors, with conflicting results: suppression in non-neural tumors, stimulation in medulloblastomas. Working with two clones of chromaffin-neuronal PC12 cells, which express different levels of REST, and using genetic complementation and knockdown approaches, we show that REST also promotes proliferation in differentiated neural cells. Mechanistically, this occurs by a signaling pathway involving REST, the GTPase-activating protein tuberin (TSC2) and the transcription co-factor beta-catenin. In PC12 cells, raised expression of REST correlates with reduced TSC2 levels, nuclear accumulation and co-transcriptional activation of beta-catenin, and increased expression of its target oncogenes Myc and Ccnd1, which might account for the proliferation advantage and the distinct morphology. Rest transcription is also increased, unveiling the existence of a self-sustaining, feed-forward REST-TSC2-beta-catenin signaling loop that is also operative in another neural cell model, NT2/D1 cells. Transfection of REST, knockdown of TSC2 or forced expression of active beta-catenin recapitulated the biochemical, functional and morphological properties of the high-expressing REST clone in wild-type PC12 cells. Upregulation of REST promoted proliferation and phenotypic changes, thus hindering neurosecretion. The new REST-TSC2-beta-catenin signaling paradigm might have an important role in various aspects of neural cell physiology and pathology, including the regulation of proliferation and neurosecretion.",
publisher = "Company Biologists Ltd, Cambridge",
journal = "Journal of Cell Science",
title = "A signaling loop of REST, TSC2 and beta-catenin governs proliferation and function of PC12 neural cells",
pages = "3186-3174",
number = "18",
volume = "124",
doi = "10.1242/jcs.087551"
}

Tomasoni, R., Negrini, S., Fiordaliso, S., Lazić, A., Tkatch, T., Mondino, A., Meldolesi, J.,& D'Alessandro, R.. (2011). A signaling loop of REST, TSC2 and beta-catenin governs proliferation and function of PC12 neural cells. in Journal of Cell Science
Company Biologists Ltd, Cambridge., 124(18), 3174-3186.
https://doi.org/10.1242/jcs.087551

Tomasoni R, Negrini S, Fiordaliso S, Lazić A, Tkatch T, Mondino A, Meldolesi J, D'Alessandro R. A signaling loop of REST, TSC2 and beta-catenin governs proliferation and function of PC12 neural cells. in Journal of Cell Science. 2011;124(18):3174-3186.
doi:10.1242/jcs.087551 .

Tomasoni, Romana, Negrini, Sara, Fiordaliso, Stefania, Lazić, Andrijana, Tkatch, Tatiana, Mondino, Anna, Meldolesi, Jacopo, D'Alessandro, Rosalba, "A signaling loop of REST, TSC2 and beta-catenin governs proliferation and function of PC12 neural cells" in Journal of Cell Science, 124, no. 18 (2011):3174-3186,
https://doi.org/10.1242/jcs.087551 . .

TY  - JOUR
AU  - Popović, Jelena
AU  - Lazić, Andrijana
AU  - Petrović, Isidora
AU  - Stevanović, Milena
PY  - 2010
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/430
AB  - The expression of Sox14 gene in spinal cord explants was found to be regulated by Sonic hedgehog (SHH) in a dose-dependent manner, indicating that this signaling molecule might act as a regulator of Sox14-expressing interneuron differentiation. In the present study we identified the positive control element and provided the first evidence that FOXA2 is involved in up-regulation of SOX14 expression in HepG2 and U87MG cell lines. By functional analysis we demonstrated that mutation in FOXA2 binding site reduced the SOX14 reporter construct activity, and that FOXA2 over-expression increased endogenous SOX14 protein expression. Further, we have shown that human SOX14 expression is GLI1 dependent in U87MG cells and SHH-N dependent in U87MG and HepG2 cell lines. By applying siRNA silencing of FOXA2, we have demonstrated that upregulation of endogenous SOX14 gene expression by SHH is, at least in part, mediated by FOXA2. However, our data revealed that a positive regulatory region, containing functional FOXA2 site analyzed in this study, is not involved in mediation of SHH dependent SOX14 activation. Data presented here provide the initial insight into molecular mechanism underlying tissue and developmentally specific regulation of the SOX14 gene expression.
PB  - Elsevier Science Bv, Amsterdam
T2  - Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms
T1  - Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression
EP  - 418
IS  - 5-6
SP  - 411
VL  - 1799
DO  - 10.1016/j.bbagrm.2010.01.002
ER  - 

@article{
author = "Popović, Jelena and Lazić, Andrijana and Petrović, Isidora and Stevanović, Milena",
year = "2010",
abstract = "The expression of Sox14 gene in spinal cord explants was found to be regulated by Sonic hedgehog (SHH) in a dose-dependent manner, indicating that this signaling molecule might act as a regulator of Sox14-expressing interneuron differentiation. In the present study we identified the positive control element and provided the first evidence that FOXA2 is involved in up-regulation of SOX14 expression in HepG2 and U87MG cell lines. By functional analysis we demonstrated that mutation in FOXA2 binding site reduced the SOX14 reporter construct activity, and that FOXA2 over-expression increased endogenous SOX14 protein expression. Further, we have shown that human SOX14 expression is GLI1 dependent in U87MG cells and SHH-N dependent in U87MG and HepG2 cell lines. By applying siRNA silencing of FOXA2, we have demonstrated that upregulation of endogenous SOX14 gene expression by SHH is, at least in part, mediated by FOXA2. However, our data revealed that a positive regulatory region, containing functional FOXA2 site analyzed in this study, is not involved in mediation of SHH dependent SOX14 activation. Data presented here provide the initial insight into molecular mechanism underlying tissue and developmentally specific regulation of the SOX14 gene expression.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms",
title = "Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression",
pages = "418-411",
number = "5-6",
volume = "1799",
doi = "10.1016/j.bbagrm.2010.01.002"
}

Popović, J., Lazić, A., Petrović, I.,& Stevanović, M.. (2010). Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression. in Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms
Elsevier Science Bv, Amsterdam., 1799(5-6), 411-418.
https://doi.org/10.1016/j.bbagrm.2010.01.002

Popović J, Lazić A, Petrović I, Stevanović M. Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression. in Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms. 2010;1799(5-6):411-418.
doi:10.1016/j.bbagrm.2010.01.002 .

Popović, Jelena, Lazić, Andrijana, Petrović, Isidora, Stevanović, Milena, "Tissue-specific Forkhead protein FOXA2 up-regulates SOX14 gene expression" in Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms, 1799, no. 5-6 (2010):411-418,
https://doi.org/10.1016/j.bbagrm.2010.01.002 . .

TY  - JOUR
AU  - D'Alessandro, Rosalba
AU  - Lazić, Andrijana
AU  - Meldolesi, Jacopo
PY  - 2009
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/365
AB  - The mechanism by which neurons and neurosecretory cells govern the expression and the exocytic discharge of their clear and dense-core vesicles had remained unclear until recently when studies in the neurosecretory cell model PC12 revealed these processes to be orchestrated by the transcriptional repressor neuron restrictive silencer factor (NRSF)/repressor element-1 silencing transcription factor (REST). In wild-type PC12 fully competent for neurosecretion, NRSF/REST is low. The genes of the proteins involved in neurosecretion [from the secretory to vesicle membrane and plasma membrane proteins, including the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) of exocytosis] were all repressed by increases of NRSF/REST expression to various extents when the increase was only a fewfold but were completely or almost completely repressed when the increase was large, as in spontaneously defective PC 12 clones. In the first case the dense-core vesicles were still competent for exocytosis but were smaller and less dense than in wild-type cells; in the second they were no longer visible but did reappear when the repression was attenuated by transfection of a dominant-negative construct of NRSF/REST combined with a secretory chromogranin or strengthened by treatment with a blocker of NRSF/REST-associated enzymes, the histone deacetylases.
PB  - Wiley-Blackwell, Malden
T2  - Mechanisms of Exocytosis
T1  - Expression of Dense-core Vesicles and of Their Exocytosis Are Governed by the Repressive Transcription Factor NRSF/REST
EP  - 200
SP  - 194
VL  - 1152
DO  - 10.1111/j.1749-6632.2008.03988.x
ER  - 

@article{
author = "D'Alessandro, Rosalba and Lazić, Andrijana and Meldolesi, Jacopo",
year = "2009",
abstract = "The mechanism by which neurons and neurosecretory cells govern the expression and the exocytic discharge of their clear and dense-core vesicles had remained unclear until recently when studies in the neurosecretory cell model PC12 revealed these processes to be orchestrated by the transcriptional repressor neuron restrictive silencer factor (NRSF)/repressor element-1 silencing transcription factor (REST). In wild-type PC12 fully competent for neurosecretion, NRSF/REST is low. The genes of the proteins involved in neurosecretion [from the secretory to vesicle membrane and plasma membrane proteins, including the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) of exocytosis] were all repressed by increases of NRSF/REST expression to various extents when the increase was only a fewfold but were completely or almost completely repressed when the increase was large, as in spontaneously defective PC 12 clones. In the first case the dense-core vesicles were still competent for exocytosis but were smaller and less dense than in wild-type cells; in the second they were no longer visible but did reappear when the repression was attenuated by transfection of a dominant-negative construct of NRSF/REST combined with a secretory chromogranin or strengthened by treatment with a blocker of NRSF/REST-associated enzymes, the histone deacetylases.",
publisher = "Wiley-Blackwell, Malden",
journal = "Mechanisms of Exocytosis",
title = "Expression of Dense-core Vesicles and of Their Exocytosis Are Governed by the Repressive Transcription Factor NRSF/REST",
pages = "200-194",
volume = "1152",
doi = "10.1111/j.1749-6632.2008.03988.x"
}

D'Alessandro, R., Lazić, A.,& Meldolesi, J.. (2009). Expression of Dense-core Vesicles and of Their Exocytosis Are Governed by the Repressive Transcription Factor NRSF/REST. in Mechanisms of Exocytosis
Wiley-Blackwell, Malden., 1152, 194-200.
https://doi.org/10.1111/j.1749-6632.2008.03988.x

D'Alessandro R, Lazić A, Meldolesi J. Expression of Dense-core Vesicles and of Their Exocytosis Are Governed by the Repressive Transcription Factor NRSF/REST. in Mechanisms of Exocytosis. 2009;1152:194-200.
doi:10.1111/j.1749-6632.2008.03988.x .

D'Alessandro, Rosalba, Lazić, Andrijana, Meldolesi, Jacopo, "Expression of Dense-core Vesicles and of Their Exocytosis Are Governed by the Repressive Transcription Factor NRSF/REST" in Mechanisms of Exocytosis, 1152 (2009):194-200,
https://doi.org/10.1111/j.1749-6632.2008.03988.x . .

TY  - JOUR
AU  - Lazić, Andrijana
AU  - Ferrai, Carmelo
AU  - Stucchi, Laura
AU  - Prada, Ilaria
AU  - Podini, Paola
AU  - Baba, Tadashi
AU  - Rocchi, Mariano
AU  - Meldolesi, Jacopo
AU  - D'Alessandro, Rosalba
PY  - 2009
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/350
AB  - Expression of neurosecretion by nerve cells requires the levels of the transcription repressor element-1 silencing transcription factor (REST) to be very low. However, when high-REST clones of PC12 cells, defective of neurosecretion, were fused to other high-REST, non-neurosecretory cells, some neurosecretion was recovered. To clarify the mechanism of this recovery, we fused defective PC12 cells with human lymphocytes. A cytogenetic analysis revealed all hybrid clones that recovered neurosecretion to contain a fragment of chromosome 11 including the gene encoding BHC80, a protein of one of the complexes that mediate REST repression. In these clones, REST levels were as high as in defective PC12, whereas BHC80, localized in the nucleus, was 4- to 5-fold higher. Transient transfection of defective PC12 with various amounts of BHC80 cDNA induced (1) in defective PC12, the reexpression of only neurosecretion mRNAs; (2) in defective PC12 cotransfected with the REST negative construct DNA-binding domain (to attenuate gene repression), the recovery of a weak, but complete neurosecretory phenotype, including dense-core granules and their regulated exocytosis. Chromatin immunoprecipitation and immunodepletion analyses revealed the extensive BHC80 association with REST at the genes of two neurosecretion proteins, chromograninB and SNAP25, however only in the low-REST PC12, whereas in high-REST defective PC12 no association was appreciable. In defective PC12 transfected with BHC80 some association was reestablished. Therefore, the recovery of neurosecretion observed after fusion/transfection of defective PC12 depends on the reciprocal level of BHC80 and REST, with BHC80 working as a negative modulator of REST repression. This role appears of possible cell physiological and pathological importance.
PB  - Soc Neuroscience, Washington
T2  - Journal of Neuroscience
T1  - The Rest Repression of the Neurosecretory Phenotype Is Negatively Modulated by BHC80, a Protein of the BRAF/HDAC Complex
EP  - 6307
IS  - 19
SP  - 6296
VL  - 29
DO  - 10.1523/JNEUROSCI.5943-08.2009
ER  - 

@article{
author = "Lazić, Andrijana and Ferrai, Carmelo and Stucchi, Laura and Prada, Ilaria and Podini, Paola and Baba, Tadashi and Rocchi, Mariano and Meldolesi, Jacopo and D'Alessandro, Rosalba",
year = "2009",
abstract = "Expression of neurosecretion by nerve cells requires the levels of the transcription repressor element-1 silencing transcription factor (REST) to be very low. However, when high-REST clones of PC12 cells, defective of neurosecretion, were fused to other high-REST, non-neurosecretory cells, some neurosecretion was recovered. To clarify the mechanism of this recovery, we fused defective PC12 cells with human lymphocytes. A cytogenetic analysis revealed all hybrid clones that recovered neurosecretion to contain a fragment of chromosome 11 including the gene encoding BHC80, a protein of one of the complexes that mediate REST repression. In these clones, REST levels were as high as in defective PC12, whereas BHC80, localized in the nucleus, was 4- to 5-fold higher. Transient transfection of defective PC12 with various amounts of BHC80 cDNA induced (1) in defective PC12, the reexpression of only neurosecretion mRNAs; (2) in defective PC12 cotransfected with the REST negative construct DNA-binding domain (to attenuate gene repression), the recovery of a weak, but complete neurosecretory phenotype, including dense-core granules and their regulated exocytosis. Chromatin immunoprecipitation and immunodepletion analyses revealed the extensive BHC80 association with REST at the genes of two neurosecretion proteins, chromograninB and SNAP25, however only in the low-REST PC12, whereas in high-REST defective PC12 no association was appreciable. In defective PC12 transfected with BHC80 some association was reestablished. Therefore, the recovery of neurosecretion observed after fusion/transfection of defective PC12 depends on the reciprocal level of BHC80 and REST, with BHC80 working as a negative modulator of REST repression. This role appears of possible cell physiological and pathological importance.",
publisher = "Soc Neuroscience, Washington",
journal = "Journal of Neuroscience",
title = "The Rest Repression of the Neurosecretory Phenotype Is Negatively Modulated by BHC80, a Protein of the BRAF/HDAC Complex",
pages = "6307-6296",
number = "19",
volume = "29",
doi = "10.1523/JNEUROSCI.5943-08.2009"
}

Lazić, A., Ferrai, C., Stucchi, L., Prada, I., Podini, P., Baba, T., Rocchi, M., Meldolesi, J.,& D'Alessandro, R.. (2009). The Rest Repression of the Neurosecretory Phenotype Is Negatively Modulated by BHC80, a Protein of the BRAF/HDAC Complex. in Journal of Neuroscience
Soc Neuroscience, Washington., 29(19), 6296-6307.
https://doi.org/10.1523/JNEUROSCI.5943-08.2009

Lazić A, Ferrai C, Stucchi L, Prada I, Podini P, Baba T, Rocchi M, Meldolesi J, D'Alessandro R. The Rest Repression of the Neurosecretory Phenotype Is Negatively Modulated by BHC80, a Protein of the BRAF/HDAC Complex. in Journal of Neuroscience. 2009;29(19):6296-6307.
doi:10.1523/JNEUROSCI.5943-08.2009 .

Lazić, Andrijana, Ferrai, Carmelo, Stucchi, Laura, Prada, Ilaria, Podini, Paola, Baba, Tadashi, Rocchi, Mariano, Meldolesi, Jacopo, D'Alessandro, Rosalba, "The Rest Repression of the Neurosecretory Phenotype Is Negatively Modulated by BHC80, a Protein of the BRAF/HDAC Complex" in Journal of Neuroscience, 29, no. 19 (2009):6296-6307,
https://doi.org/10.1523/JNEUROSCI.5943-08.2009 . .

TY  - JOUR
AU  - D'Alessandro, Rosalba
AU  - Lazić, Andrijana
AU  - Stucchi, Laura
AU  - Podini, Paola
AU  - Malosio, Maria Luisa
AU  - Meldolesi, Jacopo
PY  - 2008
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/336
AB  - The neurosecretory process is acquired during differentiation and can be lost en block by differentiated cells. To investigate the role of REST/NRSF, a transcription repressor, in the maintenance of the process we studied two PC12 clones, one wt and one defective, expressing low and high levels of endogenous RE-1 silencing transcription (factor) (REST), respectively. Stable transfection of constructs demonstrated that REST represses 10 genes coding for proteins of neurosecretory vesicles and their exocytosis, eight including and two lacking the REST-binding sequence, RE-1. Of these genes, those of chromogranins were strongly repressed by fewfold increases of REST, those of VAMP2 and syntaxin1a required much higher levels. Moreover, in wt cells transfected with an active construct the dense-core vesicles, still competent for regulated exocytosis, were much smaller, with lighter cores; in defective cells, the dominant-negative construct induced the rescue of many vesicle/exocytosis genes but not of those of chromogranins. Small dense-core vesicles, exocytized upon stimulation, were rescued when the construct-transfected defective cells were transfected also with chromograninA or treated with trichostatinA, a blocker of histone deacetylases. Our results identify REST, working by direct and indirect mechanisms, as the factor governing the maintenance of the neurosecretory process and the properties of dense-core vesicles in PC12 cells.
PB  - Blackwell Publishing, Oxford
T2  - Journal of Neurochemistry
T1  - Expression of the neurosecretory process in pc12 cells is governed by rest
EP  - 1383
IS  - 4
SP  - 1369
VL  - 105
DO  - 10.1111/j.1471-4159.2008.05259.x
ER  - 

@article{
author = "D'Alessandro, Rosalba and Lazić, Andrijana and Stucchi, Laura and Podini, Paola and Malosio, Maria Luisa and Meldolesi, Jacopo",
year = "2008",
abstract = "The neurosecretory process is acquired during differentiation and can be lost en block by differentiated cells. To investigate the role of REST/NRSF, a transcription repressor, in the maintenance of the process we studied two PC12 clones, one wt and one defective, expressing low and high levels of endogenous RE-1 silencing transcription (factor) (REST), respectively. Stable transfection of constructs demonstrated that REST represses 10 genes coding for proteins of neurosecretory vesicles and their exocytosis, eight including and two lacking the REST-binding sequence, RE-1. Of these genes, those of chromogranins were strongly repressed by fewfold increases of REST, those of VAMP2 and syntaxin1a required much higher levels. Moreover, in wt cells transfected with an active construct the dense-core vesicles, still competent for regulated exocytosis, were much smaller, with lighter cores; in defective cells, the dominant-negative construct induced the rescue of many vesicle/exocytosis genes but not of those of chromogranins. Small dense-core vesicles, exocytized upon stimulation, were rescued when the construct-transfected defective cells were transfected also with chromograninA or treated with trichostatinA, a blocker of histone deacetylases. Our results identify REST, working by direct and indirect mechanisms, as the factor governing the maintenance of the neurosecretory process and the properties of dense-core vesicles in PC12 cells.",
publisher = "Blackwell Publishing, Oxford",
journal = "Journal of Neurochemistry",
title = "Expression of the neurosecretory process in pc12 cells is governed by rest",
pages = "1383-1369",
number = "4",
volume = "105",
doi = "10.1111/j.1471-4159.2008.05259.x"
}

D'Alessandro, R., Lazić, A., Stucchi, L., Podini, P., Malosio, M. L.,& Meldolesi, J.. (2008). Expression of the neurosecretory process in pc12 cells is governed by rest. in Journal of Neurochemistry
Blackwell Publishing, Oxford., 105(4), 1369-1383.
https://doi.org/10.1111/j.1471-4159.2008.05259.x

D'Alessandro R, Lazić A, Stucchi L, Podini P, Malosio ML, Meldolesi J. Expression of the neurosecretory process in pc12 cells is governed by rest. in Journal of Neurochemistry. 2008;105(4):1369-1383.
doi:10.1111/j.1471-4159.2008.05259.x .

D'Alessandro, Rosalba, Lazić, Andrijana, Stucchi, Laura, Podini, Paola, Malosio, Maria Luisa, Meldolesi, Jacopo, "Expression of the neurosecretory process in pc12 cells is governed by rest" in Journal of Neurochemistry, 105, no. 4 (2008):1369-1383,
https://doi.org/10.1111/j.1471-4159.2008.05259.x . .