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PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells.
Toxicology. 2015 Aug 06; 334:72-80.T

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+Show Affiliations

Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.Department of Neurology, the Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China.State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan Province, China.Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China.Department of Anatomy and Neurobiology, University of Kentucky, School of Medicine, Lexington, KY, USA.Department of Pediatrics, the Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China. Electronic address: llzhao2011@qq.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26070385

Citation

Dai, Hongmei, et al. "PINK1/Parkin-mediated Mitophagy Alleviates Chlorpyrifos-induced Apoptosis in SH-SY5Y Cells." Toxicology, vol. 334, 2015, pp. 72-80.
Dai H, Deng Y, Zhang J, et al. PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells. Toxicology. 2015;334:72-80.
Dai, H., Deng, Y., Zhang, J., Han, H., Zhao, M., Li, Y., Zhang, C., Tian, J., Bing, G., & Zhao, L. (2015). PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells. Toxicology, 334, 72-80. https://doi.org/10.1016/j.tox.2015.06.003
Dai H, et al. PINK1/Parkin-mediated Mitophagy Alleviates Chlorpyrifos-induced Apoptosis in SH-SY5Y Cells. Toxicology. 2015 Aug 6;334:72-80. PubMed PMID: 26070385.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells. AU - Dai,Hongmei, AU - Deng,Yuanying, AU - Zhang,Jie, AU - Han,Hailong, AU - Zhao,Mingyi, AU - Li,Ying, AU - Zhang,Chen, AU - Tian,Jing, AU - Bing,Guoying, AU - Zhao,Lingling, Y1 - 2015/06/09/ PY - 2015/04/08/received PY - 2015/06/04/revised PY - 2015/06/05/accepted PY - 2015/6/14/entrez PY - 2015/6/14/pubmed PY - 2015/9/22/medline KW - Apoptosis KW - Chlorpyrifos KW - Mitophagy KW - PINK1/Parkin SP - 72 EP - 80 JF - Toxicology JO - Toxicology VL - 334 N2 - 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. SN - 1879-3185 UR - https://www.unboundmedicine.com/medline/citation/26070385/PINK1/Parkin_mediated_mitophagy_alleviates_chlorpyrifos_induced_apoptosis_in_SH_SY5Y_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(15)00111-0 DB - PRIME DP - Unbound Medicine ER -