title: RNA interference targeting α-synuclein attenuates methamphetamine-induced neurotoxicity in SH-SY5Y cells.
abstract: The protein α-synuclein (α-syn) is abundant in neurons and has been claimed to play critical roles in the pathophysiology of Parkinson's disease. Overexpression of α-syn has been shown to be toxicity in methamphetamine (METH)-induced model in vivo and in vitro which has Parkinson's-like pathology. However, the exact mechanisms underlying toxicity of α-syn mediated METH-induced neuron remain unknown. In the present study, human dopaminergic-like neuroblastoma SH-SY5Y cells were used as METH-induced model in vitro. Cell viability was found to be dramatically increased after silencing α-syn expression followed by METH treatment compared with a-syn wild-type cells and the morphological damage to cells after METH treatment was abated through knockdown of α-syn expression in this model. The expression levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2(VMAT-2) were significantly decreased and the activity/levels of reactive oxygen species (ROS), nitric oxide synthase (NOS) and nitrogen (NO) were notably increased after METH treatment. However, the changes of these expression levels were reversed in cells transfected with α-syn-shRNA. These results suggested that TH, DAT, VMAT-2, ROS and NOS maybe involved in α-syn mediated METH-induced neuronal toxicity.
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China. chenlingpzy@yahoo.com.cn
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Enping
authors.initials: E
authors.lastname: Huang
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.forename: Pingming
authors.initials: P
authors.lastname: Qiu
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D055785:Gene Knockdown Techniques; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; D008694:Methamphetamine