Downregulation of beclin 1 restores arsenite-induced impaired autophagic flux by improving the lysosomal function in the brain.

Arsenite is a toxic metalloid that causes various adverse effects in the brain. However, the underlying mechanisms of arsenite-induced neurotoxicity remain poorly understood. In this study, both adult beclin 1+/+ and beclin 1+/- mice were employed to establish a model of chronic arsenite exposure by treating with arsenite via drinking water for 6 months. The results clearly demonstrated that exposure to arsenite profoundly caused damage to the cerebral cortex, induced autophagy and impaired autophagic flux in the cerebral cortex. Heterozygous disruption of beclin 1 in animals remarkably alleviated the neurotoxic effects of arsenite. To verify the results obtained in the animals, a permanent U251 cell line was used. After treating of cells with arsenite, similar phenomenon was also observed, showing the significant elevation in the expression levels of autophagy-related genes. Importantly, lysosomal dysfunction caused by arsenite was observed in vitro and in vivo. Either knockdown of beclin 1 in cells or heterozygous disruption of beclin 1 in animals remarkably alleviated the lysosomal dysfunction induced by arsenite. These findings indicate that downregulation of beclin 1 could restore arsenite-induced impaired autophagic flux possibly through improving lysosomal function, and correct that regulation of autophagy via beclin 1 would be an alternative approach for the treatment of arsenite neurotoxicity. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Hongmei Zhou, Hong Ling, Yunlong Li, Xuejun Jiang, Shuqun Cheng, Golamaully Mohammad Zubeir, Yinyin Xia, Xia Qin, Jun Zhang, Zhen Zou, Chengzhi Chen. Downregulation of beclin 1 restores arsenite-induced impaired autophagic flux by improving the lysosomal function in the brain. Ecotoxicology and environmental safety. 2022 Jan 01;229:113066

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PMID: 34929507

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