Inorganic arsenic induces pyroptosis and pancreatic β cells dysfunction through stimulating the IRE1α/TNF-α pathway and protective effect of taurine. (March 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Food and chemical toxicology. Volume 125(2019)
• Page Start: 392
• Page End: 402
• Publication Date: 2019-03
• Subjects: Inorganic arsenic -- β cells dysfunction -- Taurine -- Tumor necrosis factor-α -- Pyroptosis; As2O3 arsenic trioxide -- FCM flow cytometry -- IAs inorganic arsenic -- IL-1β interleukin-1β -- IRE1α inositol-requiring enzyme 1 alpha -- KRB Krebs-Ringer Bicarbonate Solution -- LPS lipopolysaccharides -- LDH lactate dehydrogenase -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- NLRP3 NOD-like receptor family pyrin domain-containing 3 -- PI propidium iodide -- Tau taurine -- TNF-α tumor necrosis factor-α; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2019.01.015
• Languages: English
• ISSNs: 0278-6915

Abstract

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 (As2 O3 ) induced β cells dysfunction and related mechanisms are still uncertain. Here, we found that Tau relieved As2 O3 -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, As2 O3 -induced activation of pyroptosis was decreased; with tumor necrosis factor-α (TNF-α) inhibitor pretreatment, As2 O3 -induced activation of NLRP3 inflammasome and pyroptosis were decreased; further, with the inositol-requiring enzyme 1 alpha (IRE1α) inhibitor, As2 O3 -induced induction of TNF-α was decreased. Tau markedly protected As2 O3 -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 As2 O3 -induced β cell dysfunction. Moreover, TNF-α was a critical signaling node that linked As2 O3 -induced ER stress and pyroptosis. Tau was an effective supplement against As2 O3 -induced β cells dysfunction through the pathway as mentioned above. Graphical abstract: The related mechanisms of Tau attenuated As 2 O 3 -induced β cells dysfunction. Chronic exposure to As2 O3 induced phosphorylation of IRE1α and production of TNF-α. Increased TNF-α caused the activation of NLRP3 inflammasome, which led to IL-1β maturation and INS-1 cells pyroptosis.Image 1 Highlights: As2 O3 caused pyroptosis and β cells dysfunction via an IRE1α/TNF -α pathway. Taurine attenuated As2 O3 -induced pyroptosis and β cells dysfunction. Taurine downregulated the levels of IRE1α and TNF-α and decreased the activation of NLRP3-inflammasome induced by As2 O3 .