Inhibition of hydrogen sulfide generation contributes to 1-methy-4-phenylpyridinium ion-induced neurotoxicity.
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.
Tang
Xiao-Qing
XQ
Department of Physiology, Medical College, University of South China, 28 W. Changsheng Road, Hengyang, Hunan, People's Republic of China. txq01001@gmail.com
Fan
Li-Li
LL
Li
Yu-Juan
YJ
Shen
Xin-Tian
XT
Zhuan
Yuan-Yuan
YY
He
Jian-Qin
JQ
Xu
Jin-Hua
JH
Hu
Bi
B
Li
Yuan-Jian
YJ
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
D017382:Reactive Oxygen Species; D015655:1-Methyl-4-phenylpyridinium; D006862:Hydrogen Sulfide