PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells

被引：66

作者：

Dai, Hongmei ^{[1
]}

Deng, Yuanying ^{[1
]}

Zhang, Jie ^{[2
]}

Han, Hailong ^{[3
]}

Zhao, Mingyi ^{[1
]}

Li, Ying ^{[1
]}

Zhang, Chen ^{[1
]}

Tian, Jing ^{[1
]}

Bing, Guoying ^{[4
]}

Zhao, Lingling ^{[1
]}

机构：

[1] Cent S Univ, Dept Pediat, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

[2] Cent S Univ, Dept Neurol, Xiangya Hosp 2, Changsha 410013, Hunan, Peoples R China

[3] Cent S Univ, State Key Lab Med Genet, Changsha 410013, Hunan, Peoples R China

[4] Univ Kentucky, Sch Med, Dept Anat & Neurobiol, Lexington, KY 40536 USA

来源：

TOXICOLOGY | 2015年 / 334卷

关键词：

Apoptosis; Chlorpyrifos; Mitophagy; PINK1/Parkin; MITOCHONDRIAL FISSION; PESTICIDE EXPOSURE; PRENATAL EXPOSURE; AUTOPHAGY; DISEASE; PARKIN; PINK1; NEUROTOXICITY; MECHANISMS; DYNAMICS;

D O I：

10.1016/j.tox.2015.06.003

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Chlorpyrifos (CPF) is one of the most widely used organophosphorous insecticides. There are links between CPF exposure and neurological disorders. Mitochondrial damage has been implicated to play a key role in CPF-induced neurotoxicity. Mitophagy, the selective autophagic elimination of mitochondria, is an important mitochondrial quality control mechanism. However, the role of mitophagy in CPF-induced neurotoxicity remains unclear. In this study, CPF-caused mitochondrial damage, role and mechanism of mitophagy on CPF-induced neuroapoptosis were extensively studied by using SH-SY5Y cells. We showed that CPF treatment caused mitochondrial fragmentation, excessive ROS generation and mitochondrial depolarization, thus led to cell apoptosis. Moreover, CPF treatment also resulted in increased colocalizaton of mitochondria with LC3, decreased levels of mitochondrial proteins, PINK1 stabilization and mitochondrial accumulation of Parkin. These data suggested that CPF treatment induced PINK1/Parkin-mediated mitophagy in SH-SY5Y cells. Furthermore, knockdown of Parkin dramatically increased CPF-induced neuroapoptosis. On the other hand, overexpression of Parkin markedly alleviated CPF-induced SH-SY5Y cell apoptosis. Together, these findings implicate a protective role of PINK1/Parkin-mediated mitophagy against neuroapoptosis and that enhancing mitophagy provides a potential therapeutic strategy for CPF-induced neurological disorders. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.

引用

页码：72 / 80

页数：9

共 32 条

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