Department of Emergency, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Department of Emergency, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Toxicol In Vitro. 2018 Dec;53:148-159. doi: 10.1016/j.tiv.2018.08.009. Epub 2018 Aug 23.
Paraquat (PQ) is one of the most popular herbicides and has been widely used all over the world over the past several decades. However, PQ exposure can cause multiple organ failure, especially acute lung injury in humans as well as in rodent animals. Mitochondrial dysfunction plays a crucial role in PQ-induced lung cell damage. Mitophagy, defined as the selective autophagic elimination process of mitochondria, is a significant mechanism controlling mitochondrial quality. In this study, we investigated PINK1/Parkin-mediated mitophagy activated in the process of the PQ-induced cell apoptosis by using human lung epithelial-like A549 cells. We showed that PQ inhibited cell viability and induced mitochondrial damage as well as cell apoptosis in A549 cells. During this process, PQ induced PINK1/Parkin-mediated mitophagy. Knocking down the expression of Parkin gene by the transient transfection of Parkin small interfering RNA mitigated PQ-induced mitophagy and worsened A549 cell apoptosis. On the contrary, overexpression of Parkin attenuated PQ-induced cell injury by promoting mitophagy. These results indicated PINK1/Parkin-mediated mitophagy played a protective role in PQ-induced A549 cell damage and provided a potential therapeutic strategy for enhancing mitophagy against PQ poisoning.
百草枯（PQ）是最受欢迎的除草剂之一，在过去几十年中已在全球范围内广泛使用。然而，PQ 暴露会导致多器官衰竭，特别是在人类和啮齿动物中会引起急性肺损伤。线粒体功能障碍在 PQ 诱导的肺细胞损伤中起关键作用。自噬，定义为线粒体的选择性自噬消除过程，是控制线粒体质量的重要机制。在这项研究中，我们使用人肺上皮样 A549 细胞研究了 PINK1/Parkin 介导的自噬在 PQ 诱导的细胞凋亡过程中的激活。结果表明，PQ 抑制 A549 细胞活力并诱导线粒体损伤和细胞凋亡。在此过程中，PQ 诱导 PINK1/Parkin 介导的自噬。通过瞬时转染 Parkin 小干扰 RNA 敲低 Parkin 基因减轻了 PQ 诱导的自噬并加重了 A549 细胞凋亡。相反，过表达 Parkin 通过促进自噬减轻了 PQ 诱导的细胞损伤。这些结果表明 PINK1/Parkin 介导的自噬在 PQ 诱导的 A549 细胞损伤中起保护作用，并为增强自噬对抗 PQ 中毒提供了一种潜在的治疗策略。
