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

Pei, Pei, Yao, Xiaofeng, Jiang, Liping, Qiu, Tianming, Wang, Ningning, Yang, Lei, Gao, Ni, Wang, Zhidong, Yang, Guang, Liu, Xiaofang, Liu, Shuang, Jia, Xue, Tao, Ye, Wei, Sen, Sun, Xiance
Food and chemical toxicology 2019 v.125 pp. 392-402
arsenic, arsenic oxide, drinking water, endoplasmic reticulum, inflammasomes, inflammation, islets of Langerhans, phosphorylation, protective effect, rats, risk factors, taurine, tumor necrosis factor-alpha
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.