Lin Pengfei, Chen Fenglei, Sun Jin, Zhou Jinhua, Wang Xiangguo, Wang Nan, Li Xiao, Zhang Zhe, Wang Aihua, Jin YaPing
Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
Reprod Toxicol. 2015 Apr;52:71-7. doi: 10.1016/j.reprotox.2015.02.007. Epub 2015 Feb 23.
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 lentivirus-encoded 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.
玉米赤霉烯酮（ZEN）是一种镰刀菌属霉菌毒素，可导致多种生殖障碍和基因毒性效应。本研究证明内质网（ER）应激参与了ZEN诱导的小鼠睾丸间质细胞死亡。我们的研究表明，ZEN以剂量依赖的方式降低了小鼠睾丸间质肿瘤细胞系中的细胞增殖。半胱天冬酶-3活性测定结果进一步证实了凋亡是ZEN诱导细胞死亡的主要原因，该结果显示细胞死亡呈ZEN剂量依赖性增加。用ZEN处理MLTC-1细胞和原代小鼠睾丸间质细胞会上调ER应激典型标志物GRP78、CHOP和半胱天冬酶-12蛋白的表达。此外，用4-苯基丁酸预处理细胞或使用慢病毒编码的短发夹RNA敲低GRP78可显著减少ZEN诱导的凋亡，并抑制CHOP和半胱天冬酶-12的表达。总之，这些结果表明ER应激途径的激活在ZEN诱导的小鼠睾丸间质细胞凋亡中起关键作用。
