The role of Fas-FasL-FADD signaling pathway in arsenic-mediated neuronal apoptosis in vivo and in vitro

Hongna Sun; Yanmei Yang; Muyu Gu; Yang Li; Zhe Jiao; Chunqing Lu; Bingyu Li; Yuting Jiang; Lixin Jiang; Fang Chu; Wenjing Yang; Dianjun Sun; Yanhui Gao

doi:10.1016/j.toxlet.2021.11.012

The role of Fas-FasL-FADD signaling pathway in arsenic-mediated neuronal apoptosis in vivo and in vitro

Toxicol Lett. 2022 Mar 1:356:143-150. doi: 10.1016/j.toxlet.2021.11.012. Epub 2021 Dec 22.

Authors

Hongna Sun¹, Yanmei Yang¹, Muyu Gu², Yang Li¹, Zhe Jiao¹, Chunqing Lu¹, Bingyu Li¹, Yuting Jiang¹, Lixin Jiang³, Fang Chu¹, Wenjing Yang¹, Dianjun Sun⁴, Yanhui Gao⁵

Affiliations

¹ 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.
² School of Public Health, Tianjin Medical University, Tianjin, China.
³ Harbin Medical University Cancer Hospital, Harbin, China.
⁴ 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. Electronic address: hrbmusdj@163.com.
⁵ 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. Electronic address: gaoyanhui@hrbmu.edu.cn.

PMID: 34953944
DOI: 10.1016/j.toxlet.2021.11.012

Abstract

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.

Keywords: Apoptosis; Arsenic; Fas-FasL-FADD signal pathway; Neurone; ZB4.

MeSH terms

Animals
Arsenic / administration & dosage
Arsenic / toxicity*
Caspase 3 / genetics
Caspase 3 / metabolism
Caspase 8 / genetics
Caspase 8 / metabolism
Cell Line, Tumor
Dose-Response Relationship, Drug
Environmental Pollutants / toxicity
Fas Ligand Protein / genetics
Fas Ligand Protein / metabolism*
Fas-Associated Death Domain Protein / genetics
Fas-Associated Death Domain Protein / metabolism*
Gene Expression Regulation / drug effects
Humans
Male
Neurons / drug effects*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Random Allocation
Rats
Rats, Sprague-Dawley
Signal Transduction / drug effects
Up-Regulation
fas Receptor / genetics
fas Receptor / metabolism*

Substances

Environmental Pollutants
Fadd protein, rat
Fas Ligand Protein
Fas protein, rat
Fas-Associated Death Domain Protein
RNA, Messenger
fas Receptor
Casp8 protein, rat
Caspase 3
Caspase 8
Arsenic