衔接蛋白SH2B1β可减少过氧化氢诱导的PC12细胞和海马神经元的细胞死亡。
The adaptor protein SH2B1β reduces hydrogen peroxide-induced cell death in PC12 cells and hippocampal neurons.
作者信息
Lu Wan-Chen, Chen Chien-Jen, Hsu Hui-Chien, Hsu Hsin-Ling, Chen Linyi
机构信息
Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan.
出版信息
J Mol Signal. 2010 Sep 27;5:17. doi: 10.1186/1750-2187-5-17.
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.
背景
SH2B1β是一种信号衔接蛋白，已被证明可促进PC12细胞中的神经元分化，并且是交感神经元存活所必需的。然而，SH2B1β影响细胞存活的机制尚不清楚。
结果
在本研究中，我们研究了SH2B1β在氧化应激诱导的细胞死亡中的作用。我们的结果表明，过表达SH2B1β可减少H2O2诱导的PC12细胞和海马神经元中依赖半胱天冬酶3的凋亡。响应H2O2，过表达SH2B1β增强了PI3K（磷脂酰肌醇3激酶）-AKT（蛋白激酶B）和MEK（MAPK/ERK激酶）-细胞外信号调节激酶1和2（ERK1/2）信号通路。我们进一步证明，SH2B1β能够减少H2O2诱导的FoxO1和3a转录因子的核定位，这两种转录因子位于PI3K-AKT和MEK-ERK-ERK1/2通路的下游。此外，过表达SH2B1β降低了Fas配体（FasL）的表达，FasL是FoxOs的靶基因之一。
结论
过表达衔接蛋白SH2B1β增强了H2O2诱导的PI3K-AKT和MEK-ERK1/2信号传导，减少了核定位的FoxOs和促凋亡基因FasL的表达。
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