2. Academic Validation
  3. Mechanism of arsenic regulation of mitochondrial damage and autophagy induced synaptic damage through SIRT1 and protective effect of melatonin in HT22 cell

Mechanism of arsenic regulation of mitochondrial damage and autophagy induced synaptic damage through SIRT1 and protective effect of melatonin in HT22 cell

  • Chem Biol Interact. 2025 May 1:412:111461. doi: 10.1016/j.cbi.2025.111461.
Xiaoli Zhang 1,  Jing Wang 2,  Shuyuan Li 2,  Kun Chen 2,  Longmei Wang 2,  Chao Feng 2,  Yi Gao 3,  Xiaoyan Yan 3,  Qian Zhao 3,  Ben Li 3,  Jinping Zheng 4,  Yulan Qiu 5
Affiliations

Affiliations

  • 1 Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China; Department of Microbiology Laboratory, Linfen Central Hospital, Linfen, 041000, Shanxi, China; Section of Occupational Medicine, Department of Special Medicine, Shanxi Medical University, Taiyuan, 030001, Shanxi, China; Key Laboratory of Shanxi Province for Aging Mechanism Research and Transformation, Center for Healthy Aging, Changzhi Medical College, Changzhi, 046000, Shanxi, China.
  • 2 Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
  • 3 Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China; MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
  • 4 Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China; Section of Occupational Medicine, Department of Special Medicine, Shanxi Medical University, Taiyuan, 030001, Shanxi, China; Key Laboratory of Shanxi Province for Aging Mechanism Research and Transformation, Center for Healthy Aging, Changzhi Medical College, Changzhi, 046000, Shanxi, China. Electronic address: zheng_jp@sxmu.edu.cn.
  • 5 Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China; MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. Electronic address: ylqiu@sxmu.edu.cn.
PMID: 40081728 DOI: 10.1016/j.cbi.2025.111461
Abstract

Arsenic (As), a widespread environmental pollutant, can induce severe neurological damage worldwide; however, the underlying mechanisms remain unclear. Sirtuin 1 (SIRT1) has been reported to exert neuroprotective effects against various neurological diseases by resisting mitochondrial damage and Autophagy through deacetylation. In this study, we established a model of HT22 cells exposed to NaAsO2 and examined the levels of mitochondrial, Autophagy, and synaptic damage in HT22 cells and HT22 cells with high expression of SIRT1 (pre-treated with the agonist SRT1720) 24 h after exposure. Our results suggest that NaAsO2 exposure induces down-regulation of SIRT1, causing mitochondrial damage and activation of Autophagy, which in turn leads to synaptic damage. Notably, melatonin (Mel) intervention upregulated SIRT1 and attenuated mitochondrial damage and Autophagy, restoring synaptic damage. In conclusion, the results of the present study indicate that As causes neurotoxicity by decreasing SIRT1 production, causing mitochondrial damage and activating Autophagy, which provides fundamental data for further study of arsenic neurotoxicity. In addition, blocking this pathway attenuated the synaptic damage of arsenic exposure, which provides a new therapeutic avenue for arsenic neurotoxicity.

Keywords

Arsenic; Autophagy; Mitochondria; SIRT1; Synaptic damage.

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