Department of Stem Cell and Regenerative Biology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 05029, Korea.
Department of Swine & Poultry Science, Korea National College of Agriculture and Fisheries, 1515, Kongjwipatjwi-ro, Deokjin-gu, Jeonju-si 54874, Jeollabuk-do, Korea.
Toxins (Basel). 2022 Feb 17;14(2):148. doi: 10.3390/toxins14020148.
Zearalenone (ZEN), a widely known mycotoxin, is mainly produced by various species, and it is a potent estrogenic metabolite that affects reproductive health in livestock and humans. In this study, the molecular mechanisms of toxicity and cell damage induced by ZEN in GC-1 spermatogonia (spg) cells were evaluated. Our results showed that cell viability decreased and apoptosis increased in a dose-dependent manner when GC-1 spg cells were exposed to ZEN. In addition, the key proteins involved in apoptosis, cleaved caspase-3 and -8, BAD, BAX, and phosphorylation of p53 and ERK1/2, were significantly increased in ZEN-exposed GC-1 spg cells for 24 h, and cytochrome c was released from mitochondria by ZEN. Interestingly, ZEN also triggered autophagy in GC-1 spg cells. The expression levels of the autophagy-related genes Atg5, Atg3, Beclin 1, LC3, Ulk1, Bnip 3, and p62 were significantly higher in ZEN-treated GC-1 spg cells, and the protein levels of both LC3A/B and Atg12 were remarkably increased in a dose-dependent manner in ZEN-exposed GC-1 spg cells compared to the control. In addition, immunostaining results showed that ZEN-treated groups showed a remarkable increase in LC 3A/B positive puncta as compared to the control in a dose-dependent manner based on confocal microscopy analysis in GC-1 spg cells. Our findings suggest that ZEN has toxic effects on tGC-1 spg cells and induces both apoptosis and autophagy.
玉米赤霉烯酮（ZEN）是一种广泛存在的真菌毒素，主要由多种真菌产生，是一种具有强大雌激素活性的代谢物，会影响家畜和人类的生殖健康。在本研究中，评估了 ZEN 对 GC-1 精原细胞（spg）细胞毒性和细胞损伤的分子机制。结果显示，GC-1 spg 细胞暴露于 ZEN 后，细胞活力呈剂量依赖性降低，细胞凋亡增加。此外，在暴露于 ZEN 的 24 h 内，凋亡相关关键蛋白，如 cleaved caspase-3 和 -8、BAD、BAX、p53 和 ERK1/2 的磷酸化，以及线粒体中的细胞色素 c 明显增加。有趣的是，ZEN 还会引发 GC-1 spg 细胞自噬。在 ZEN 处理的 GC-1 spg 细胞中，自噬相关基因 Atg5、Atg3、Beclin 1、LC3、Ulk1、Bnip 3 和 p62 的表达水平明显升高，LC3A/B 和 Atg12 的蛋白水平也明显升高，呈剂量依赖性。此外，免疫染色结果显示，与对照组相比，基于共聚焦显微镜分析，ZEN 处理组的 LC 3A/B 阳性斑点明显增加，呈剂量依赖性。这些发现表明 ZEN 对 tGC-1 spg 细胞具有毒性作用，并诱导细胞凋亡和自噬。
