1. Academic Validation
  2. Inorganic arsenic induces pyroptosis and pancreatic β cells dysfunction through stimulating the IRE1α/TNF-α pathway and protective effect of taurine

Inorganic arsenic induces pyroptosis and pancreatic β cells dysfunction through stimulating the IRE1α/TNF-α pathway and protective effect of taurine

  • Food Chem Toxicol. 2019 Mar;125:392-402. doi: 10.1016/j.fct.2019.01.015.
Pei Pei 1 Xiaofeng Yao 1 Liping Jiang 2 Tianming Qiu 1 Ningning Wang 3 Lei Yang 1 Ni Gao 1 Zhidong Wang 1 Guang Yang 3 Xiaofang Liu 3 Shuang Liu 1 Xue Jia 1 Ye Tao 1 Sen Wei 1 Xiance Sun 4
Affiliations

Affiliations

  • 1 Department of Occupational and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, 116044, PR China.
  • 2 Experimental Teaching Center of Public Health, Dalian Medical University, 9 Lvshun South Road, Dalian, 116044, PR China.
  • 3 Nutrition and Food Hygiene, Dalian Medical University, 9 Lvshun South Road, Dalian, 116044, PR China.
  • 4 Department of Occupational and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, 116044, PR China; Global Health Research Center, Dalian Medical University, 9 Lvshun South Road, Dalian, 116044, PR China. Electronic address: sunxiance@dmu.edu.cn.
Abstract

Low-level inorganic arsenic (iAs) in drinking water is a risk factor for β cells dysfunction. Taurine (Tau) is a kind of semi-essential β amino acid, and beneficial for β cell function. However, the effects of Tau on arsenic trioxide (As2O3) induced β cells dysfunction and related mechanisms are still uncertain. Here, we found that Tau relieved As2O3-induced endoplasmic reticulum (ER) stress, inflammation and Pyroptosis in rat pancreas. In INS-1 cells, with NOD-like receptor family pyrin domain-containing 3 (NLRP3) inhibitor pretreatment, As2O3-induced activation of Pyroptosis was decreased; with tumor necrosis factor-α (TNF-α) inhibitor pretreatment, As2O3-induced activation of NLRP3 inflammasome and Pyroptosis were decreased; further, with the inositol-requiring Enzyme 1 alpha (IRE1α) inhibitor, As2O3-induced induction of TNF-α was decreased. Tau markedly protected As2O3-induced β cells dysfunction by reducing the phosphorylation of IRE1α, production of TNF-α, activation of NLRP3 inflammasome and Pyroptosis. Our results revealed that ER stress dependent inflammation and Pyroptosis are critical pathogenic components of As2O3-induced β cell dysfunction. Moreover, TNF-α was a critical signaling node that linked As2O3-induced ER stress and Pyroptosis. Tau was an effective supplement against As2O3-induced β cells dysfunction through the pathway as mentioned above.

Keywords

Inorganic arsenic; Pyroptosis; Taurine; Tumor necrosis factor-α; β cells dysfunction.

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