Bai Jie, Yao Xiaofeng, Jiang Liping, Qiu Tianming, Liu Shuang, Qi Baoxu, Zheng Yue, Kong Yuan, Yang Guang, Chen Min, Liu Xiaofang, Sun Xiance
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
Biochimie. 2016 Apr;123:1-6. doi: 10.1016/j.biochi.2016.01.002. Epub 2016 Jan 14.
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.
砷越来越被认为是2型糖尿病的一个风险因素。在我们之前的研究中，我们发现无机砷刺激自噬通量并通过活性氧途径在INS-1细胞中导致自噬性细胞死亡。由于核因子E2相关因子2（Nrf2）和硫氧还蛋白（Trx）系统是对抗活性氧的关键防线，我们在本研究中调查了Nrf2/Trx途径是否促成了三氧化二砷刺激的自噬以及牛磺酸在其中的作用。用2mg/kg体重 - 8mg/kg体重的三氧化二砷处理57天后，后代胰腺中Nrf2蛋白的表达显著降低。随后胰腺中Trx基因的表达也显著降低。最后，活性氧的产生刺激了砷处理的胰腺中的自噬。牛磺酸可以逆转砷对Nrf2和Trx的抑制并抑制自噬。简而言之，Nrf2/Trx途径的抑制可能在砷相关糖尿病的发病机制中起重要作用。在高砷暴露地区，牛磺酸可作为预防砷相关糖尿病的营养补充剂。
