title: Role of aldehyde dehydrogenase 2 in 1-methy-4-phenylpyridinium ion-induced aldehyde stress and cytotoxicity in PC12 cells.
abstract: Aldehyde stress contributes to molecular mechanisms of cell death and the pathogenesis of Parkinson's disease (PD). The neurotoxin 1-Methy-4-Phenylpyridinium Ion (MPP(+)) is commonly used to model PD. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme detoxifying aldehydes. The aim of this study is to evaluate whether MPP(+)-induced neurotoxicity is involved in aldehyde stress by modulation of ALDH2. Our results demonstrated that treatment of PC12 cells with MPP(+) leads to aldehyde stress by increasing in loads of malondialdehyde and 4-hydroxynonenal, which indicated that MPP(+)-induced aldehyde stress contributes to its cytotoxicity in PC12 cells. We also showed that MPP(+) up-regulates the expression and activity of ALDH2 in PC12 cells and that inhibition of ALDH2 by its specific inhibitor daidzin prevents MPP(+)-induced decrease in cell viability and increases in apoptosis, oxidative stress and aldehyde stress in PC12 cells. These findings suggest that aldehyde stress contributes to MPP(+)-induced toxicity in PC12 cells by upregulation of ALDH2. This study provides a novel insight into the role of ALDH2 in the neurotoxicity of MPP(+).
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, 336 E Dongfeng Road, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Wei-Lan
authors.initials: WL
authors.lastname: Yin
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats
chemical_list: D000447:Aldehydes; D004791:Enzyme Inhibitors; D007529:Isoflavones; D024101:Mitochondrial Proteins; C013908:daidzin; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; D015655:1-Methyl-4-phenylpyridinium