title: S-Nitrosylating protein disulphide isomerase mediates α-synuclein aggregation caused by methamphetamine exposure in PC12 cells.
abstract: Methamphetamine (METH) belongs to Amphetamine-type stimulants, METH abusers are at high risk of neurodegenerative disorders, including Parkinson's disease (PD). However, there are still no effective treatments to METH-induced neurodegeneration because its mechanism remains unknown. In order to investigate METH's neurotoxic mechanism, we established an in vitro PD pathology model by exposing PC12 cells to METH. We found the expression of nitric oxide synthase (NOS), nitric oxide (NO) and α-synuclein (α-syn) was significantly increased after METH treatment for 24h, in addition, the aggregattion of α-syn and the S-nitrosylation of protein disulphideisomerase(PDI) were also obviously enhanced. When we exposed PC12 cells to the NOS inhibitor N-nitro-L-arginine(L-NNA) with METH together, the L-NNA obviously inhibited these changes induced by METH. While when we exposed PC12 cells to the precursor of NO L-Arginine together with METH, the L-Arginine resulted in the opposite effect compared to L-NNA. And when we knocked down the PDI gene, the L-NNA did not have this effect. Therefore, PDI plays a significant role in neurological disorders related to α-syn aggregation, and it suggests that PDI could be as a potential target to prevent METH-induced neurodegeneration.
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China. Electronic address: 13512783934@163.com.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Wu
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China.
authors.forename: Ai-Feng
authors.initials: AF
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China.
authors.forename: En-Ping
authors.initials: EP
authors.lastname: Huang
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China.
authors.forename: Wei-Bing
authors.initials: WB
authors.lastname: Xie
authors.affiliation: Guangzhou Forensic Science Institute, Guangzhou, Guangdong Province 510030, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China.
authors.forename: Wei-Ye
authors.initials: WY
authors.lastname: Huang
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China.
authors.forename: Chuan-Xiang
authors.initials: CX
authors.lastname: Chen
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China. Electronic address: qiupm@163.com.
authors.forename: Ping-Ming
authors.initials: PM
authors.lastname: Qiu
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China. Electronic address: hjwang711@163.com.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D008694:Methamphetamine / Q000633:toxicity*; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D016716:PC12 Cells; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D051381:Rats; D013997:Time Factors; D014162:Transfection; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; C497606:Snca protein, rat; D051844:alpha-Synuclein; D019335:Nitroarginine; D009569:Nitric Oxide; D008694:Methamphetamine; D019001:Nitric Oxide Synthase; D019704:Protein Disulfide-Isomerases
keywords: Methamphetamine; Neurodegeneration; Parkinson's disease; Protein disulphideisomerase; α-synuclein