GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+
Само за регистроване кориснике
2010
Чланак у часопису (Објављена верзија)
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Gamma-amminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system of vertebrates, serves as an autocrine/paracrine signaling molecule during development, modulating a number of calcium (Ca2+)-dependent processes, including proliferation, migration, and differentiation, acting via 2 types of GABA receptors (GABARs): ionotropic GABA(A)Rs and metabotropic GABA(B)Rs. Here, we demonstrate that mouse embryonic stem cells (mESCs), which possess the capacity for virtually unlimited self-renewal and pluripotency, synthesize GABA and express functional GABA(A)Rs and GABA(B)Rs, as well as voltage-gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inwardly rectifying potassium (GIRK) channels. On activation, both GABAR types triggered synergistically intracellular calcium rise. Muscimol (a GABA(A)R agonist) induced single Ca2+ transients involving both VGCC-mediated Ca2+ influx and intracellular stores, while baclofen (a GABA(B)R agonist) evoked Ca2+... transients followed by intercellular Ca2+ waves and oscillations that were resistant to antagonists and entirely dependent on Ca2+ release from intracellular stores. Prolonged treatment with muscimol slightly inhibited, while baclofen or SR95531 (a GABA(A)R antagonist) significantly facilitated, mESC proliferation. GABA(A)R-specific ligands also induced morphological and gene expression changes indicating a differentiation shift. Our data suggest that the interplay between GABARs and downstream (coupled) effectors differentially modulates mESC proliferation/differentiation through selective activation of second messenger signaling cascades.-Schwirtlich, M., Emri, Z., Antal, K., Mate, Z., Katarova, Z., Szabo, G. GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+. FASEB J. 24, 1218-1228 (2010). www.fasebj.org
Кључне речи:
ES cell self-renewal/differentiation / connexin 43 / Ca2+ imagingИзвор:
FASEB Journal, 2010, 24, 4, 1218-1228Издавач:
- Federation Amer Soc Exp Biol, Bethesda
DOI: 10.1096/fj.09-143586
ISSN: 0892-6638
PubMed: 19959723
WoS: 000276462300028
Scopus: 2-s2.0-77951637809
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Schwirtlich, Marija AU - Emri, Zsuzsa AU - Antal, Karoly AU - Mate, Zoltan AU - Katarova, Zoya AU - Szabo, Gabor PY - 2010 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/420 AB - Gamma-amminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system of vertebrates, serves as an autocrine/paracrine signaling molecule during development, modulating a number of calcium (Ca2+)-dependent processes, including proliferation, migration, and differentiation, acting via 2 types of GABA receptors (GABARs): ionotropic GABA(A)Rs and metabotropic GABA(B)Rs. Here, we demonstrate that mouse embryonic stem cells (mESCs), which possess the capacity for virtually unlimited self-renewal and pluripotency, synthesize GABA and express functional GABA(A)Rs and GABA(B)Rs, as well as voltage-gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inwardly rectifying potassium (GIRK) channels. On activation, both GABAR types triggered synergistically intracellular calcium rise. Muscimol (a GABA(A)R agonist) induced single Ca2+ transients involving both VGCC-mediated Ca2+ influx and intracellular stores, while baclofen (a GABA(B)R agonist) evoked Ca2+ transients followed by intercellular Ca2+ waves and oscillations that were resistant to antagonists and entirely dependent on Ca2+ release from intracellular stores. Prolonged treatment with muscimol slightly inhibited, while baclofen or SR95531 (a GABA(A)R antagonist) significantly facilitated, mESC proliferation. GABA(A)R-specific ligands also induced morphological and gene expression changes indicating a differentiation shift. Our data suggest that the interplay between GABARs and downstream (coupled) effectors differentially modulates mESC proliferation/differentiation through selective activation of second messenger signaling cascades.-Schwirtlich, M., Emri, Z., Antal, K., Mate, Z., Katarova, Z., Szabo, G. GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+. FASEB J. 24, 1218-1228 (2010). www.fasebj.org PB - Federation Amer Soc Exp Biol, Bethesda T2 - FASEB Journal T1 - GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+ EP - 1228 IS - 4 SP - 1218 VL - 24 DO - 10.1096/fj.09-143586 ER -
@article{ author = "Schwirtlich, Marija and Emri, Zsuzsa and Antal, Karoly and Mate, Zoltan and Katarova, Zoya and Szabo, Gabor", year = "2010", abstract = "Gamma-amminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system of vertebrates, serves as an autocrine/paracrine signaling molecule during development, modulating a number of calcium (Ca2+)-dependent processes, including proliferation, migration, and differentiation, acting via 2 types of GABA receptors (GABARs): ionotropic GABA(A)Rs and metabotropic GABA(B)Rs. Here, we demonstrate that mouse embryonic stem cells (mESCs), which possess the capacity for virtually unlimited self-renewal and pluripotency, synthesize GABA and express functional GABA(A)Rs and GABA(B)Rs, as well as voltage-gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inwardly rectifying potassium (GIRK) channels. On activation, both GABAR types triggered synergistically intracellular calcium rise. Muscimol (a GABA(A)R agonist) induced single Ca2+ transients involving both VGCC-mediated Ca2+ influx and intracellular stores, while baclofen (a GABA(B)R agonist) evoked Ca2+ transients followed by intercellular Ca2+ waves and oscillations that were resistant to antagonists and entirely dependent on Ca2+ release from intracellular stores. Prolonged treatment with muscimol slightly inhibited, while baclofen or SR95531 (a GABA(A)R antagonist) significantly facilitated, mESC proliferation. GABA(A)R-specific ligands also induced morphological and gene expression changes indicating a differentiation shift. Our data suggest that the interplay between GABARs and downstream (coupled) effectors differentially modulates mESC proliferation/differentiation through selective activation of second messenger signaling cascades.-Schwirtlich, M., Emri, Z., Antal, K., Mate, Z., Katarova, Z., Szabo, G. GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+. FASEB J. 24, 1218-1228 (2010). www.fasebj.org", publisher = "Federation Amer Soc Exp Biol, Bethesda", journal = "FASEB Journal", title = "GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+", pages = "1228-1218", number = "4", volume = "24", doi = "10.1096/fj.09-143586" }
Schwirtlich, M., Emri, Z., Antal, K., Mate, Z., Katarova, Z.,& Szabo, G.. (2010). GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+. in FASEB Journal Federation Amer Soc Exp Biol, Bethesda., 24(4), 1218-1228. https://doi.org/10.1096/fj.09-143586
Schwirtlich M, Emri Z, Antal K, Mate Z, Katarova Z, Szabo G. GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+. in FASEB Journal. 2010;24(4):1218-1228. doi:10.1096/fj.09-143586 .
Schwirtlich, Marija, Emri, Zsuzsa, Antal, Karoly, Mate, Zoltan, Katarova, Zoya, Szabo, Gabor, "GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+" in FASEB Journal, 24, no. 4 (2010):1218-1228, https://doi.org/10.1096/fj.09-143586 . .