title: Sodium arsenite induces ROS-dependent autophagic cell death in pancreatic β-cells.
abstract: Inorganic arsenic is a worldwide environmental pollutant. Inorganic arsenic's positive relationship with the incidence of type 2 diabetes mellitus arouses concerns associated with its etiology in diabetes among the general human population. In this study, the inhibitor of autophagosome formation, 3-methyladenine, protected the cells against sodium arsenite cytotoxicity, and the autophagy stimulator rapamycin further decreased the cell viability of sodium arsenite-treated INS-1 cells. These finding suggested the hypothesis that autophagic cell death contributed to sodium arsenite-induced cytotoxicity in INS-1 cells. Sodium arsenite increased the autophagosome-positive puncta in INS-1 cells observed under a fluorescence microscope, and this effect was confirmed by the elevated LC3-II levels detected through Western blot. The LC3 turnover assay indicated that the accumulation of autophagosomes in the arsenite-treated INS-1 cells was due to increased formation rather than impaired degradation. The pretreatment of INS-1 cells with the ROS inhibitor NAC reduced autophagosome formation and reversed the sodium arsenite cytotoxicity, indicating that sodium arsenite-induced autophagic cell death was ROS-dependent. In summary, the precise molecular mechanisms through which arsenic is related to diabetes have not been completely elucidated, but the ROS-dependent autophagic cell death of pancreatic β-cells described in this study may help to elucidate the underlying mechanism.
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
authors.forename: Xue-Xin
authors.initials: XX
authors.lastname: Zhu
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yao
authors.affiliation: Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, 9 W Lvshun South Road, Dalian 116044, PR China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jiang
authors.affiliation: Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, 9 W Lvshun South Road, Dalian 116044, PR China.
authors.forename: Cheng-Yan
authors.initials: CY
authors.lastname: Geng
authors.affiliation: Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, 9 W Lvshun South Road, Dalian 116044, PR China.
authors.forename: Lai-Fu
authors.initials: LF
authors.lastname: Zhong
authors.affiliation: Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, 9 W Lvshun South Road, Dalian 116044, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
authors.forename: Bai-Lu
authors.initials: BL
authors.lastname: Zheng
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China; Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, 9 W Lvshun South Road, Dalian 116044, PR China. Electronic address: sunxiance@gmail.com.
authors.forename: Xian-Ce
authors.initials: XC
authors.lastname: Sun
mesh_terms: D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017670:Sodium Compounds / Q000633:toxicity*
chemical_list: D018053:Arsenites; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; C017947:sodium arsenite
keywords: Autophagy; INS-1 cell; Reactive oxygen species; Sodium arsenite