Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 70, Issue -, Pages 144-150Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2014.05.006
Keywords
Sodium arsenite; Autophagy; Reactive oxygen species; INS-1 cell
Categories
Funding
- National Natural Science Foundation of China (NSFC) [30972562, 30600488]
- Program for Liaoning Excellent Talents in University (LNET) [LJQ2011096]
- Liaoning BaiQianWan Talents Program [2009921030]
Ask authors/readers for more resources
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 MAC 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 beta-cells described in this study may help to elucidate the underlying mechanism. (C) 2014 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available