1. Academic Validation
  2. TNF-α derived from arsenite-induced microglia activation mediated neuronal necroptosis

TNF-α derived from arsenite-induced microglia activation mediated neuronal necroptosis

  • Ecotoxicol Environ Saf. 2022 May 1;236:113468. doi: 10.1016/j.ecoenv.2022.113468.
Huanhuan Wang 1 Yao Chen 1 Xudan Liu 1 Ruo Zhang 1 Xiaotong Wang 1 Qianhui Zhang 1 Yuting Wei 1 Fang Fang 1 Ye Yuan 1 Qianqian Zhou 1 Yinqiao Dong 1 Sainan Shi 1 Xiaojing Jiang 1 Xin Li 2
Affiliations

Affiliations

  • 1 Department of Occupational and Environmental Health, Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, School of Public Health, China Medical University, Shenyang 110122, China.
  • 2 Department of Occupational and Environmental Health, Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address: xli75@cmu.edu.cn.
Abstract

Arsenic, an identified environmental toxicant, poses threats to the health of human beings through contaminated water and food. Recently, increasing reports focused on arsenic-induced nerve damage, however, the underlying mechanism remains elusive. Microglia are important immune cells in the nervous system, which produce a large number of inflammatory factors including TNF-α when activated. Recent reports indicated that TNF-α is involved in the process of Necroptosis, a new type of programmed cell death discovered recently. Although there were evidences suggested that arsenic could induce both microglia activation and TNF-α production in the nervous system, the mechanism of arsenic-induced neurotoxicity due to microglia activation is rarely studied. In addition, the role of microglia-derived TNF-α in response to arsenic exposure in Necroptosis has not been documented before. In this study, we found that arsenite induced microglial activation through p38 MAPK signaling pathway, leading to the production of TNF-α. Microglia-derived TNF-α further induced Necroptosis in the neuronal cells. Our findings suggested that Necroptosis induced by microglia-derived TNF-α upon arsenite exposure partially played a role in arsenic-induced cell death which underlie the fundamental event of arsenic-related neurotoxicity.

Keywords

Arsenic; Microglia; Necroptosis; Neurotoxicity; TNF-α.

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