The aggravating effect of selenium deficiency on T-2 toxin-induced damage on primary cardiomyocyte results from a reduction of protective autophagy
The aggravating effect of selenium deficiency on T-2 toxin-induced damage on primary cardiomyocyte results from a reduction of protective autophagy
复制标题
缺硒会加重 T-2 毒素诱导的原代心肌细胞损伤，这是由于保护性自噬减少所致。
DOI：
10.1016/j.cbi.2019.01.009
复制
发表时间：
2019-02-25
影响因子：
5.1
通讯作者：
Huang, Kehe
中科院分区：
文献类型：
--
作者：
Chen, Xingxiang;Xu, Jing;Huang, Kehe
硒缺乏和T-2毒素暴露可能是克山病以充血性心肌病为特征的发病因素。本研究旨在探讨自噬在缺硒加重T-2毒素对原代心肌细胞损伤中的作用。我们目前的研究表明，0.25-1 μ M的T-2毒素损伤的原代心肌细胞和硒缺乏加剧T-2毒素诱导的损伤，通过测量MTT，乳酸脱氢酶和切割的caspase 3的水平。T-2毒素引发原代心肌细胞自噬，如通过显著增加LC 3-II和Beclin-1 mRNA水平的表达所指示的。雷帕霉素（自噬激动剂）处理增加自噬水平并降低T-2毒素引起的细胞毒性，而3-甲基腺嘌呤（自噬抑制剂）处理降低自噬水平并增强T-2毒素的细胞毒性，表明自噬保护原代心肌细胞免受T-2毒素的细胞毒性。硒缺乏降低T-2毒素处理的原代心肌细胞的细胞保护性自噬。由此可见，T-2毒素诱导的自噬具有保护原代心肌细胞的作用，但缺硒会降低保护性自噬，从而加剧T-2毒素诱导的损伤。本研究结果可部分解释缺硒与T-2毒素在克山病发病中的联合作用。
Selenium deficiency and T-2 toxin exposure may contribute to the development of Keshan disease characterized by congestive cardiomyopathy. The aim of this study was to explore the role of autophagy in the aggravation of selenium deficiency on T-2 toxin-induced damages on primary cardiomyocyte. Our present study demonstrated that 0.25-1 mu M T-2 toxin damaged primary cardiomyocytes and selenium deficiency exacerbated T-2 toxin-induced damages by measuring the levels of MTT, lactate dehydrogenase and cleaved-caspase 3. T-2 toxin triggered autophagy in primary cardiomyocytes, as indicated by markedly increased expressions of LC3-II and Beclin-1 mRNA levels. Rapamycin (autophagy agonist) treatment increased autophagy levels and decreased the cytotoxicity caused by T-2 toxin while 3-methyladenine (autophagy inhibitor) treatment reduced autophagy levels and enhanced the cytotoxicity of T-2 toxin, suggesting that autophagy protect primary cardiomyocytes from the cytotoxicity of T-2 toxin. Selenium deficiency lowered cytoprotective autophagy in the primary cardiomyocytes treated by T-2 toxin. It can be concluded that autophagy induced by T-2 toxin plays a role in protecting primary cardiomyocyte, but selenium deficiency decreases the protective autophagy and then exacerbate T-2 toxin-induced damages. Our finding may partly interpret the combination effects of selenium deficiency and T-2 toxin on the development of Keshan disease.