期刊
TOXICOLOGY IN VITRO
卷 34, 期 -, 页码 212-219出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2016.04.006
关键词
Manganese; Mitophagy; PINK1; Parkin; SH-SY5Y cell
类别
资金
- National Natural Science Foundation of China (NSFC) [30972502, 81172693]
- Beijing Natural Science Foundation [7152084]
Manganese (Mn) as an environmental risk factor of Parkinson's:disease (PD) is considered to cause manganism. Mitophagy is thought to play a key role in elimination the injured mitochondria. The goal of this paper was to explore whether the PINK1/Parkin-mediated mitophagy is activated and its role in Mn-induced 'mitochondria' dysfunction and cell death in SH-SY5Y cells. Here, we investigated effects of MnCl2 on ROS generation, mitochondrial membrane potential (MMP/Delta psi(m)) and apoptosis by FACS and examined PINK1/Parkin-mediated mitophagy by western-blotting and the co-localization of mitochondria and acidic lysosomes. Further, we explore the role of mitophagy in Mn-induced apoptosis by inhibition the mitophagy by knockdown Parkin level. Results show that MnCl2 dose-dependently caused Delta psi(m) decrease, ROS generation and apoptosis of dopaminergic SH-SY5Y cells. Moreover, Mn could induce mitophagy and PINK1/Parkin-mediated pathway was activated in SH-SY5Y cells. Transient transfection of Parkin siRNA knockdown the expressing level of parkin inhibited Mn-induced mitophagy and aggravated apoptosis of SH-SY5Y cells. In conclusion, our study demonstrated that Mn may induce PINK1/Parkin-mediated mitophagy, :which may exert significant neuro-protective effect against Mn-induced dopaminergic neuronal cells apoptosis. (C) 2016 Elsevier Ltd. All rights reserved.
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