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Food Chem Toxicol. 2014 Aug;70:144-50. doi: 10.1016/j.fct.2014.05.006. Epub 2014 May 21.

Sodium arsenite induces ROS-dependent autophagic cell death in pancreatic β-cells.

Author information

1
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
2
Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, 9 W Lvshun South Road, Dalian 116044, PR China.
3
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.

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.

KEYWORDS:

Autophagy; INS-1 cell; Reactive oxygen species; Sodium arsenite

PMID:
24859355
DOI:
10.1016/j.fct.2014.05.006
[Indexed for MEDLINE]

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