NDLI: Endogenous Hydrogen Sulfide is Involved in Asymmetric Dimethylarginine-induced Protection Against Neurotoxicity of 1-Methyl-4-phenyl-pyridinium Ion

Content Provider	Springer Nature Link
Author	Tang, Xiao Qing Fang, Heng Rong Li, Yu Juan Zhou, Cheng Fang Ren, Yan Kai Chen, Rong Qian Wang, Chun Yan Hu, Bi
Copyright Year	2011
Abstract	Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, is profoundly protective against 1-methy-4-phenylpyridinium ion (MPP$^{+}$)-induced neurotoxicity. Reactive oxygen species (ROS) overproduction contributes to the neurotoxicity of MPP$^{+}$; while hydrogen sulfide (H$_{2}$S) is a pivotal endogenous antioxidant. This study is to assess the potential role of endogenous H$_{2}$S in the neuroprotection of ADMA against MPP$^{+}$-induced toxicity in PC12 cells. We showed that ADMA prevented MPP$^{+}$-induced inhibition of endogenous H$_{2}$S generation through inhibiting the down-regulation of cystathionine-β-synthetase (CBS, the major enzyme responsible for endogenous H$_{2}$S generation in PC12 cells) expression and activity elicited by MPP$^{+}$. ADMA obviously attenuated MPP$^{+}$-triggered accumulation of intracellular ROS, dissipation of mitochondrial membrane potential (MMP), release of cytochrome c (Cyt-c), and downregulation of Bcl-2 protein expression in PC12 cells. Inhibition of CBS activity by amino-oxyacetate and CBS silencing with a short hairpin RNA vector targeting rat CBS gene reversed the protective action of ADMA against MPP$^{+}$-caused cytotoxicity, ROS overproduction, and MMP loss in PC12 cells. These results indicate that the protection of ADMA against MPP$^{+}$-mediated neurotoxicity involves the melioration of MPP$^{+}$-induced inhibition of endogenous H$_{2}$S generation. Our findings suggest that modulation of H$_{2}$S production provide new therapeutic targets for the treatment of neurodegenerative disease, such as Parkinson’s disease.
Starting Page	2176
Ending Page	2185
Page Count	10
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	36
Issue Number	11
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2011-07-07
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Hydrogen sulfide Asymmetric dimethylarginine Neuroprotection 1-Methy-4-phenylpyridinium ion Reactive oxygen species Neurochemistry Neurosciences Neurology Cell Biology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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