Taurine protects against As2O3-induced autophagy in pancreas of rat offsprings through Nrf2/Trx pathway

Biochimie. 2016 Apr:123:1-6. doi: 10.1016/j.biochi.2016.01.002. Epub 2016 Jan 14.

Abstract

Arsenic was increasingly to blame as a risk factor for type 2 diabetes mellitus. In our previous study, we had found iAs stimulated autophagic flux and caused autophagic cell death through ROS pathway in INS-1 cells. Since NF-E2-related factor 2 (Nrf2) and the thioredoxin (Trx) system was a crucial line of defense against ROS, we investigated whether Nrf2/Trx pathway contributed to As2O3-stimulated autophagy and the role of taurine in this study. After treatment with 2 mg/kg BW-8 mg/kg BW As2O3 for 57 d, the expression of Nrf2 protein was decreased significantly in offsprings' pancreas. The expression of Trx gene was decreased significantly in pancreas subsequently. Finally, the generation of reactive oxygen species stimulated autophagy in arsenic-treated pancreas. Taurine could reverse arsenic-inhibited Nrf2 and Trx and inhibit autophagy. In short, inhibition of Nrf2/Trx pathway might play an important role in the pathogenesis of arsenic-related diabetes. Taurine could serve as nutrition supplementation against arsenic-related diabetes in high arsenic exposure area.

Keywords: As(2)O(3); Autophagy; Nrf2; Taurine; Trx.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arsenic Trioxide
  • Arsenicals
  • Autophagy / drug effects*
  • Gene Expression Regulation / drug effects
  • Malondialdehyde / metabolism
  • NF-E2-Related Factor 2 / metabolism*
  • Oxides / toxicity*
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Rats
  • Taurine / pharmacology*
  • Thioredoxins / genetics
  • Thioredoxins / metabolism*

Substances

  • Arsenicals
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Oxides
  • Taurine
  • Malondialdehyde
  • Thioredoxins
  • Arsenic Trioxide