Neurotoxicity Research

, Volume 19, Issue 3, pp 403–411 | Cite as

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

  • Xiao-Qing Tang
  • Li-Li Fan
  • Yu-Juan Li
  • Xin-Tian Shen
  • Yuan-Yuan Zhuan
  • Jian-Qin He
  • Jin-Hua Xu
  • Bi Hu
  • Yuan-Jian Li
Article

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.

Keywords

Hydrogen sulfide 1-Methy-4-phenylpyridinium ion Cystathionine-β-synthetase PC12 cells Neurotoxicity 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Xiao-Qing Tang
    • 1
    • 2
  • Li-Li Fan
    • 1
  • Yu-Juan Li
    • 1
  • Xin-Tian Shen
    • 1
    • 3
  • Yuan-Yuan Zhuan
    • 1
  • Jian-Qin He
    • 1
  • Jin-Hua Xu
    • 4
  • Bi Hu
    • 1
  • Yuan-Jian Li
    • 2
  1. 1.Department of Physiology, Medical CollegeUniversity of South ChinaHengyangPeople’s Republic of China
  2. 2.Department of Pharmacology, School of Pharmaceutical SciencesCentral South UniversityChangshaPeople’s Republic of China
  3. 3.Department of PhysiologyHuaihua Medical CollegeHuaihuaPeople’s Republic of China
  4. 4.Laboratory Center of Biochemistry and Molecular BiologyUniversity of South ChinaHengyangPeople’s Republic of China

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