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首页> 外文期刊>Reproductive toxicology >Mycotoxin zearalenone induces apoptosis in mouse Leydig cells via an endoplasmic reticulum stress-dependent signalling pathway
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Mycotoxin zearalenone induces apoptosis in mouse Leydig cells via an endoplasmic reticulum stress-dependent signalling pathway

机译:霉菌毒素玉米赤霉烯酮通过内质网应激依赖性信号通路诱导小鼠睾丸间质细胞凋亡

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摘要

Zearalenone (ZEN) is a Fusarium mycotoxin that causes several reproductive disorders and genotoxic effects. This study demonstrated the involvement of endoplasmic reticulum (ER) stress in ZEN-induced mouse Leydig cell death. Our study showed that ZEN reduced cell proliferation in a murine Leydig tumour cell line in a dose-dependent manner. The involvement of apoptosis as a major cause of ZEN-induced cell death was further confirmed by the results of a caspase-3 activity assay, which showed a ZEN dose-dependent increase in cell death. Treatment of MLTC-1 and primary mouse Leydig cells with ZEN upregulated the expression of the ER stress-typical markers GRP78, CHOP and caspase-12 protein. Further, pre-treating the cells with 4-phenylbutyrate or knocking down GRP78 using lentivirusencoded shRNA significantly diminished ZEN-induced apoptosis and inhibited the expression of CHOP and caspase-12. In summary, these results suggest that the activation of an ER stress pathway plays a key role in ZEN-induced apoptosis in the mouse Leydig cells. (C) 2015 Elsevier Inc. All rights reserved.
机译:玉米赤霉烯酮(ZEN)是一种镰刀菌霉菌毒素,可引起多种生殖疾病和遗传毒性。这项研究表明内质网(ER)应激参与ZEN诱导的小鼠Leydig细胞死亡。我们的研究表明ZEN以剂量依赖性方式减少了鼠Leydig肿瘤细胞系中的细胞增殖。 caspase-3活性测定的结果进一步证实了凋亡是ZEN诱导的细胞死亡的主要原因,这表明ZEN剂量依赖性地增加了细胞死亡。 ZEN处理MLTC-1和原代小鼠Leydig细胞可上调ER应激典型标志物GRP78,CHOP和caspase-12蛋白的表达。此外,用4-苯基丁酸酯预处理细胞或使用慢病毒编码的shRNA敲低GRP78可显着减少ZEN诱导的凋亡,并抑制CHOP和caspase-12的表达。总之,这些结果表明,ER应激途径的激活在ZEN诱导的小鼠Leydig细胞凋亡中起着关键作用。 (C)2015 Elsevier Inc.保留所有权利。

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