Suppressor of cytokine signaling 1 protects rat pancreatic islets from cytokine-induced apoptosis through Janus kinase/signal transducers and activators of transcription pathway / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 4048-4053, 2013.
Article
em En
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| ID: wpr-236107
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WPRO
ABSTRACT
<p><b>BACKGROUND</b>Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathway involved in negative feedback loops. Although SOCS1 is an important intracellular suppressor of apoptosis in a variety of cell types, its role in cytokine-induced pancreatic β-cell apoptosis remains unclear. The present study investigated potential effects of SOCS1 on the cytokine-induced pancreatic β-cell apoptosis.</p><p><b>METHODS</b>After successfully transfected with SOCS1/pEGFP-C1 or pEGFP-C1 plasmids to overexpress SOCS1, RINm5F (rat insulinoma cell line) cells were exposed to cytokines, interferon (IFN)-γ alone, IFN-γ+interleukin (IL)-1β, IFN-β+IL-1β+tumor necrosis factor (TNF)-α respectively. Pancreatic β-cell apoptosis was assessed by using MTT, FACS, and caspase-3 activity assays. Protein phosphorylation of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1 (STAT1) were verified by Western blotting and mRNA expression of inducible nitric oxide synthase (iNOS), NF-κB and Fas were analyzed by RT-PCR.</p><p><b>RESULTS</b>Overexpression of SOCS1 in RINm5F cells was shown to attenuate IFN-γ alone, IFN-γ+IL-1β and IFN-γ+TNF-α+IL-1β mediated apoptosis. Phosphorylation of JAK2 and STAT1 significantly decreased in RINm5F cells which overexpressed SOCS1 protein. Overexpression of SOCS1 significantly suppressed cytokine-induced iNOS mRNA levels.</p><p><b>CONCLUSION</b>Overexpression of SOCS1 protects pancreatic islets from cytokine-induced cell apoptosis via the JAK2/STAT1 pathway.</p>
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Assunto principal:
Farmacologia
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Fosforilação
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Transdução de Sinais
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Linhagem Celular
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Western Blotting
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Citocinas
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Ilhotas Pancreáticas
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Interferon gama
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Interleucina-1
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Fator de Necrose Tumoral alfa
Limite:
Animals
Idioma:
En
Revista:
Chinese Medical Journal
Ano de publicação:
2013
Tipo de documento:
Article