Journal
MOLECULAR PHARMACOLOGY
Volume 75, Issue 1, Pages 27-34Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/mol.108.047985
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Funding
- Singapore National Medical Research Council [1057/2006]
- Singapore Biomedical Research Council [07/1/21/19/509]
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Hydrogen sulfide (H2S) has been proposed as a novel neuro-modulator, 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 (Delta Psi(m)) 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 (mitoK(ATP)) 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 mitoK(ATP) channel/ p38- and JNK-MAPK pathway. Our data suggest that H2S may have potential therapeutic value for neurodegenerative diseases, such as PD.
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