TY - JOUR T1 - Hydrogen Sulfide Inhibits Rotenone-Induced Apoptosis via Preservation of Mitochondrial Function JF - Molecular Pharmacology JO - Mol Pharmacol SP - 27 LP - 34 DO - 10.1124/mol.108.047985 VL - 75 IS - 1 AU - Li-Fang Hu AU - Ming Lu AU - Zhi-Yuan Wu AU - Peter T.-H. Wong AU - Jin-Song Bian Y1 - 2009/01/01 UR - http://molpharm.aspetjournals.org/content/75/1/27.abstract N2 - Hydrogen sulfide (H2S) has been proposed as a novel neuromodulator, which plays critical roles in the central nervous system affecting both neurons and glial cells. However, its relationship with neurodegenerative diseases is unexplored. The present study was undertaken to investigate the effects of H2S on cell injury induced by rotenone, a commonly used toxin in establishing in vivo and in vitro Parkinson's disease (PD) models, in human-derived dopaminergic neuroblastoma cell line (SH-SY5Y). We report here that sodium hydrosulfide (NaHS), an H2S donor, concentration-dependently suppressed rotenone-induced cellular injury and apoptotic cell death. NaHS also prevented rotenone-induced p38- and c-Jun NH2-terminal kinase (JNK)-mitogen-activated protein kinase (MAPK) phosphorylation and rotenone-mediated changes in Bcl-2/Bax levels, mitochondrial membrane potential (ΔΨm) dissipation, cytochrome c release, caspase-9/3 activation and poly(ADP-ribose) polymerase cleavage. Furthermore, 5-hydroxydecanoate, a selective blocker of mitochondrial ATP-sensitive potassium (mitoKATP) channel, attenuated the protective effects of NaHS against rotenone-induced cell apoptosis. Thus, we demonstrated for the first time that H2S inhibited rotenone-induced cell apoptosis via regulation of mitoKATP channel/p38- and JNK-MAPK pathway. Our data suggest that H2S may have potential therapeutic value for neurodegenerative diseases, such as PD. The American Society for Pharmacology and Experimental Therapeutics ER -