College of Food Science and Engineering, Northwest A & F University, Yangling 712100, China.
Toxins (Basel). 2021 Aug 26;13(9):595. doi: 10.3390/toxins13090595.
Patulin (PAT) belongs to the family of food-borne mycotoxins. Our previous studies revealed that PAT caused cytotoxicity in human embryonic kidney cells (HEK293). In the present research, we systematically explored the detailed mechanism of ROS production and ROS clearance in PAT-induced HEK293 cell apoptosis. Results showed that PAT treatment (2.5, 5, 7.5, 10 μM) for 10 h could regulate the expression of genes and proteins involved in the mitochondrial respiratory chain complex, resulting in dysfunction of mitochondrial oxidative phosphorylation and induction of ROS overproduction. We further investigated the role of -acetylcysteine (NAC), an ROS scavenger, in promoting the survival of PAT-treated HEK293 cells. NAC improves PAT-induced apoptosis of HEK293 cells by clearing excess ROS, modulating the expression of mitochondrial respiratory chain complex genes and proteins, and maintaining normal mitochondrial function. In addition, NAC protects the activity of antioxidant enzymes, maintains normal GSH content, and relieves oxidative damage. Additionally, 4 mM NAC alleviated 7.5 μM PAT-mediated apoptosis through the caspase pathway in HEK293 cells. In summary, our study demonstrated that ROS is significant in PAT-mediated cytotoxicity, which provides valuable insight into the management of PAT-associated health issues.
棒曲霉素（PAT）属于食源性病原体毒素家族。我们之前的研究表明，棒曲霉素会导致人胚肾细胞（HEK293）的细胞毒性。在本研究中，我们系统地探讨了 ROS 产生和 ROS 清除在 PAT 诱导的 HEK293 细胞凋亡中的详细机制。结果表明，PAT 处理（2.5、5、7.5、10 μM）10 h 可以调节线粒体呼吸链复合物相关基因和蛋白的表达，导致线粒体氧化磷酸化功能障碍和 ROS 过度产生。我们进一步研究了 ROS 清除剂 N-乙酰半胱氨酸（NAC）在促进 PAT 处理的 HEK293 细胞存活中的作用。NAC 通过清除过量的 ROS、调节线粒体呼吸链复合物基因和蛋白的表达以及维持正常的线粒体功能，改善了 PAT 诱导的 HEK293 细胞凋亡。此外，NAC 保护抗氧化酶的活性，维持正常的 GSH 含量，并减轻氧化损伤。此外，4 mM 的 NAC 通过 caspase 途径缓解了 7.5 μM 的 PAT 介导的 HEK293 细胞凋亡。总之，我们的研究表明 ROS 在 PAT 介导的细胞毒性中起重要作用，这为管理与 PAT 相关的健康问题提供了有价值的见解。
