Hydrogen sulfide inhibits rotenone-induced apoptosis via preservation of mitochondrial function.
Mol Pharmacol. 2008 Oct 2;
Authors: Hu LF, Lu M, Wu ZY, Wong PT, Bian J
Hydrogen sulfide (H2S) has been proposed as a novel neuromodulator, which plays critical roles in the central nervous system (CNS) 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 JNK- MAPK phosphorylation and rotenone-mediated changes in Bcl-2/Bax levels, mitochondrial membrane potential (DeltaPsim) dissipation, cytochrome c release, caspase-9/3 activation and poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore, 5-hydroxydecanoate (5-HD), 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- & JNK-MAPK pathway. Our data suggest that H2S may have potential therapeutic value for neurodegenerative diseases, such as PD. Key words: neuroprotection; cytochrome c; caspase-9/3; mitoKATP channel; p38/JNK MAPK.
PMID: 18832435 [PubMed - as supplied by publisher]