國家衛生研究院 NHRI:Item 3990099045/5202
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    題名: The adaptor protein SH2B1Beta reduces hydrogen peroxide-induced cell death in PC12 cells and hippocampal neurons
    其他題名: The adaptor protein SH2B1β reduces hydrogen peroxide-induced cell death in PC12 cells and hippocampal neurons
    作者: Lu, WC;Chen, CJ;Hsu, HC;Hsu, HL;Chen, L
    貢獻者: Division of Molecular and Genomic Medicine
    摘要: Background: SH2B1β is a signaling adaptor protein that has been shown to promote neuronal differentiation in PC12 cells and is necessary for the survival of sympathetic neurons. However, the mechanism by which SH2B1β may influence cell survival is not known.Results: In this study, we investigated the role of SH2B1β in oxidative stress-induced cell death. Our results suggest that overexpressing SH2B1β reduced H2O2-induced, caspase 3-dependent apoptosis in PC12 cells and hippocampal neurons. In response to H2O2, overexpressing SH2B1β enhanced PI3K (phosphatidylinositol 3-kinas)- AKT (protein kinase B) and MEK (MAPK/ERK kinase)-extracellular-signal regulated kinases 1 and 2 (ERK1/2) signaling pathways. We further demonstrated that SH2B1β was able to reduce H2O2-induced nuclear localization of FoxO1 and 3a transcription factors, which lie downstream of PI3K-AKT and MEK-ERK1/2 pathways. Moreover, overexpressing SH2B1β reduced the expression of Fas ligand (FasL), one of the target genes of FoxOs. Conclusions: Overexpressing the adaptor protein SH2B1β enhanced H2O2-induced PI3K-AKT and MEK-ERK1/2 signaling, reduced nucleus-localized FoxOs and the expression of a pro-apoptotic gene, FasL.
    日期: 2010-09-27
    關聯: Journal of Molecular Signaling. 2010 Sep;5:Article number 17.
    Link to: http://dx.doi.org/10.1186/1750-2187-5-17
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77957118047
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