自噬
FOXO3公司
蛋白激酶B
氧化应激
PI3K/AKT/mTOR通路
细胞生物学
LY294002型
福克斯O1
信号转导
活性氧
程序性细胞死亡
神经保护
化学
生物
细胞凋亡
药理学
内分泌学
生物化学
作者
Aiqing Deng,Limin Ma,Qiuhong Ji,Jiajun Xing,Jianxin Qin,Xueli Zhou,Xin Wang,Shouyan Wang,Jianjun Wu,Xia Chen
标识
DOI:10.1139/cjpp-2022-0341
摘要
Autophagy has been implicated in stroke. Our previous study showed that the FoxO3 transcription factor promotes autophagy after transient cerebral ischemia/reperfusion (I/R). However, whether the Akt/FoxO3 signaling pathway plays a regulatory role in autophagy in cerebral I/R-induced oxidative stress injury is still unclear. The present study aims to investigate the effects of the Akt/FoxO3 signaling pathway on autophagy activation and neuronal injury in vitro and in vivo. By employing LY294002 or insulin to regulate the Akt/FoxO3 signaling pathway, we found that insulin pretreatment increased cell viability, decreased reactive oxygen species production, and enhanced the expression of antiapoptotic and autophagy-related proteins following H2O2 injury in HT22 cells. In addition, insulin significantly decreased neurological deficit scores and infarct volume and increased the expression of antiapoptotic and autophagy-related proteins following I/R injury in rats. However, LY294002 showed the opposite effects under these conditions. Altogether, these results indicate that Akt/FoxO3 signaling pathway activation inhibited oxidative stress-mediated cell death through activation of autophagy. Our study supports a critical role for the Akt/FoxO3 signaling pathway in autophagy activation in stroke.
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