Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health Commission(23618504), Harbin, 150081 Heilongjiang, China.
School of Public Health, Tianjin Medical University, Tianjin, China.
Toxicol Lett. 2022 Mar 1;356:143-150. doi: 10.1016/j.toxlet.2021.11.012. Epub 2021 Dec 22.
The molecular mechanisms underlying arsenic-induced neurotoxicity have not been completely elucidated. Our study aimed to determine the role of the Fas-FasL-FADD signaling pathway in arsenic-mediated neuronal apoptosis. Pathological and molecular biological tests were performed on the cerebral cortex of arsenic-exposed rats and SH-SY5Y neuroblastoma cells. Arsenic induced apoptosis in the cortical neurons, which corresponded to abnormal ultrastructural changes. Mechanistically, arsenic activated the Fas-FasL-FADD signaling pathway and the downstream caspases both in vivo and in vitro. ZB4 treatment reversed the apoptotic effects of arsenic on the SHSY5Y cells. Taken together, arsenic induces neurotoxicity by activating the Fas-FasL-FADD signaling pathway.
砷诱导神经毒性的分子机制尚未完全阐明。本研究旨在确定 Fas-FasL-FADD 信号通路在砷介导的神经元凋亡中的作用。对暴露于砷的大鼠大脑皮层和 SH-SY5Y 神经母细胞瘤细胞进行了病理和分子生物学测试。砷诱导皮质神经元凋亡，这与异常的超微结构变化相对应。从机制上讲，砷在体内和体外均激活了 Fas-FasL-FADD 信号通路及其下游半胱天冬酶。ZB4 处理逆转了砷对 SH-SY5Y 细胞的凋亡作用。综上所述，砷通过激活 Fas-FasL-FADD 信号通路诱导神经毒性。
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