Protective effects of S-nitrosoglutathione against neurotoxicity of 3-nitropropionic acid in rat.
Mitochondrial dysfunction and oxidative stress are often linked to various neurodegenerative disorders including ischemic stroke and Huntington's disease (HD). S-Nitrosoglutathione (GSNO) is an endogenous nitric oxide carrier recently identified as a potent antioxidant capable of neutralizing oxidative stress. In the present study, we explore the neuroprotective effects of GSNO against metabolic insults induced by 3-nitropropionic acid (3-NP), a mitochondrial complex II inhibitor commonly used as a pharmacological model for HD, in primary culture of fetal rat cortical and striatal neurons. Application of GSNO (1-5 microM) substantially reduced neuronal loss caused by 3-NP (1-5 mM) exposure based on MTT reduction, lactate dehydrogenase (LDH) release, and Hoechst staining assays. The protective effect of GSNO appeared to be more potent than N-acetyl-l-cysteine (NAC), a glutathione precursor, at the same concentrations. These results suggest that manipulation of GSNO metabolism may exert protective effects against mitochondrial dysfunction often observed in neurodegenerative disorders.
Ju
Tzyh-Chwen
TC
Institute of Neuroscience, Tzu Chi University, Hualien 970, Taiwan.
Yang
Ya-Ting
YT
Yang
Ding-I
DI
D000704:Analysis of Variance; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D009574:Nitro Compounds; D011422:Propionates / Q000037:antagonists & inhibitors*; D051381:Rats; D026422:S-Nitrosoglutathione / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D013778:Tetrazolium Salts; D013844:Thiazoles; D026422:S-Nitrosoglutathione; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; C015392:3-nitropropionic acid