Arsenic induced autophagy-dependent apoptosis in hippocampal neurons via AMPK/mTOR signaling pathway
Yao Chen, Xudan Liu, Qianhui Zhang, Huanhuan Wang, Ruo Zhang, Yanhong Ge, Huning Liang, Wanying Li, Juanjun Fan, Huimin Liu, Zhengyang Lv, Wenting Dou, Yì Wáng, Xin Li, Yì Wáng, Xin Li
Abstract
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.