title: PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells.
abstract: 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.
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Neurology, the Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan Province, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, School of Medicine, Lexington, KY, USA.
authors.forename: Guoying
authors.initials: G
authors.lastname: Bing
authors.affiliation: Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China. Electronic address: llzhao2011@qq.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D063306:Mitophagy; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D000099202:PTEN-Induced Putative Kinase
chemical_list: D004390:Chlorpyrifos; D007306:Insecticides; D008869:Microtubule-Associated Proteins; D011494:Protein Kinases; D017382:Reactive Oxygen Species; D000099202:PTEN-Induced Putative Kinase; C477012:MAP1LC3A protein, human
keywords: Apoptosis; Chlorpyrifos; Mitophagy; PINK1/Parkin