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Inhibition of Hydrogen Sulfide Generation Contributes to 1-Methy-4-Phenylpyridinium Ion-Induced Neurotoxicity

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Abstract

Reactive oxygen species (ROS) overproduction contributes to the neurotoxicity of 1-methy-4-phenylpyridinium ion (MPP+). Increasing studies have shown that hydrogen sulfide (H2S) 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 H2S synthesis in PC12 cells, a clonal rat pheochromocytoma cell line, and whether disturbance of H2S 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 H2S generation and results in remarkable cell damage. We find that cystathionine-β-synthetase (CBS) is catalyzed in PC12 cells to generate H2S, and that both expression and activity of CBS are inhibited by MPP+ treatment. Exposure of sodium hydrosulfide (NaHS), a donor of H2S, 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 H2S 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.

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Acknowledgments

We thank Y. Wang for excellent revising. This study was supported by Natural Science Foundation of China (30770740), Natural Science Foundation of Hunan Province, China (06JJ2074), China Postdoctoral Science Foundation (2005038233), Plan Project for Scientific Research, Department of Science and Technology, Hunan Province (05FJ3039), and the Research Foundation of Education Bureau of Hunan Province (06C700).

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Authors and Affiliations

  1. Department of Physiology, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People’s Republic of China

    Xiao-Qing Tang, Li-Li Fan, Yu-Juan Li, Xin-Tian Shen, Yuan-Yuan Zhuan, Jian-Qin He & Bi Hu

  2. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiangya Road, Changsha, 410078, Hunan, People’s Republic of China

    Xiao-Qing Tang & Yuan-Jian Li

  3. Department of Physiology, Huaihua Medical College, Huaihua, 418000, Hunan, People’s Republic of China

    Xin-Tian Shen

  4. Laboratory Center of Biochemistry and Molecular Biology, University of South China, Hengyang, 421001, Hunan, People’s Republic of China

    Jin-Hua Xu

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  1. Xiao-Qing Tang
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  2. Li-Li Fan
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  3. Yu-Juan Li
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Correspondence to Xiao-Qing Tang or Yuan-Jian Li.

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Xiao-Qing Tang and Li-Li Fan contributed equally to this work.

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Tang, XQ., Fan, LL., Li, YJ. et al. Inhibition of Hydrogen Sulfide Generation Contributes to 1-Methy-4-Phenylpyridinium Ion-Induced Neurotoxicity. Neurotox Res 19, 403–411 (2011). https://doi.org/10.1007/s12640-010-9180-4

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  • DOI: https://doi.org/10.1007/s12640-010-9180-4

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