title: Inhibition of hydrogen sulfide generation contributes to 1-methy-4-phenylpyridinium ion-induced neurotoxicity.
abstract: Reactive oxygen species (ROS) overproduction contributes to the neurotoxicity of 1-methy-4-phenylpyridinium ion (MPP(+)). Increasing studies have shown that hydrogen sulfide (H(2)S) is an endogenous antioxidant gas. We have hypothesized that MPP(+)-caused neurotoxicity may involve the imbalance of proportion to this endogenous protective antioxidant gas. The aim of this study is to evaluate whether MPP(+) disturbs H(2)S synthesis in PC12 cells, a clonal rat pheochromocytoma cell line, and whether disturbance of H(2)S generation induced by MPP(+) is an underlying mechanism of MPP(+)-induced neurotoxicity. We show that exposure of PC12 cells to MPP(+) causes a significant decrease in H(2)S generation and results in remarkable cell damage. We find that cystathionine-β-synthetase (CBS) is catalyzed in PC12 cells to generate H(2)S, and that both expression and activity of CBS are inhibited by MPP(+) treatment. Exposure of sodium hydrosulfide (NaHS), a donor of H(2)S, extenuates MPP(+)-induced cytotoxicity and ROS accumulation in PC12 cells, while inhibition of CBS by amino-oxyacetate (AOAA) exacerbates the effects of MPP(+). These results indicate that MPP(+) neurotoxicity involves reduction of H(2)S production, which is caused by inhibition of CBS. This study provides novel insights into cell death observed in neurodegenerative disease such as Parkinson's disease.
authors.affiliation: Department of Physiology, Medical College, University of South China, 28 W. Changsheng Road, Hengyang, Hunan, People's Republic of China. txq01001@gmail.com
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tang
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Fan
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Li
authors.forename: Xin-Tian
authors.initials: XT
authors.lastname: Shen
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhuan
authors.forename: Jian-Qin
authors.initials: JQ
authors.lastname: He
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Xu
authors.forename: Bi
authors.initials: B
authors.lastname: Hu
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D015655:1-Methyl-4-phenylpyridinium; D006862:Hydrogen Sulfide