自噬
安普克
PI3K/AKT/mTOR通路
细胞生物学
细胞凋亡
程序性细胞死亡
化学
串扰
激活剂(遗传学)
信号转导
线粒体
神经毒性
癌症研究
生物
蛋白激酶A
磷酸化
生物化学
受体
光学
物理
有机化学
毒性
作者
Yao Chen,Xudan Liu,Qianhui Zhang,Huanhuan Wang,Ruo Zhang,Yanhong Ge,Huning Liang,Wanying Li,Juanjun Fan,Huimin Liu,Zhengyang Lv,Wei Dou,Yi Wang,Xin Li
标识
DOI:10.1016/j.fct.2023.113954
摘要
Arsenic contamination of groundwater remains a serious public health problem worldwide. Arsenic-induced neurotoxicity receives increasing attention, however, the mechanism remains unclear. Hippocampal neuronal death is regarded as the main event of arsenic-induced cognitive dysfunction. Mitochondria lesion is closely related to cell death, however, the effects of arsenic on PGAM5-regulated mitochondrial dynamics has not been documented. Crosstalk between autophagy and apoptosis is complicated and autophagy has a dual role in the apoptosis pathways in neuronal cells. In this study, arsenic exposure resulted in mitochondrial PGAM5 activation and subsequent activation of apoptosis and AMPK-mTOR dependent autophagy. Intervention by autophagy activator Rapamycin or inhibitor 3-MA, both targeting at mTOR, accordingly induced activation or inhibition of apoptosis. Intervention by MK-3903 or dorsomorphin, activator or inhibitor of AMPK, received similar results. Our findings suggested that arsenic-induced PGAM5 activation played a role in AMPK-mTOR dependent autophagy and arsenic induced autophagy-dependent apoptosis in hippocampal neurons via AMPK/mTOR signaling pathway.
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