PINK1/Parkin-mediated mitophagy play a protective role in manganese induced apoptosis in SH-SY5Y cells.
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 mitochondrial dysfunction and cell death in SH-SY5Y cells. Here, we investigated effects of MnCl2 on ROS generation, mitochondrial membrane potential (MMP/ΔΨm) 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 ΔΨm 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.
Department of Toxicology, Peking University Health Science Center, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University Health Science Center, Beijing 100191, China.
Hong-Tao
HT
Zhang
Department of Toxicology, Peking University Health Science Center, Beijing 100191, China; Cancer Hospital & Institute, Peking University, Beijing 100142, China.
Lan
L
Mi
Department of Toxicology, Peking University Health Science Center, Beijing 100191, China; China-US (Henan) Hormel Cancer Institute, Zhengzhou 450003, Henan, China.
Ting
T
Wang
Medical and Health Analysis Center, Peking University, Beijing 100191, China.
Lan
L
Yuan
Department of Toxicology, Peking University Health Science Center, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University Health Science Center, Beijing 100191, China.
Xue-Hui
XH
Li
Department of Toxicology, Peking University Health Science Center, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University Health Science Center, Beijing 100191, China.
Li-Sha
LS
Dong
Department of Toxicology, Peking University Health Science Center, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University Health Science Center, Beijing 100191, China.
Peng
P
Zhao
Department of Toxicology, Peking University Health Science Center, Beijing 100191, China.
Juan-Ling
JL
Fu
Department of Toxicology, Peking University Health Science Center, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University Health Science Center, Beijing 100191, China. Electronic address: yaoby@bjmu.edu.cn.
Bi-Yun
BY
Yao
Department of Toxicology, Peking University Health Science Center, Beijing 100191, China.
Zong-Can
ZC
Zhou
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008345:Manganese / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D063306:Mitophagy / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
D008345:Manganese; D011494:Protein Kinases; D017382:Reactive Oxygen Species; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein
Manganese; Mitophagy; PINK1; Parkin; SH-SY5Y cell