Hydrogen Sulfide Inhibits Rotenone-Induced Apoptosis via Preservation of Mitochondrial Function

作者：Hu Li Fang; Lu Ming; Wu Zhi Yuan; Wong Peter T H; Bian Jin Song^*

来源：Molecular Pharmacology, 2009, 75(1): 27-34.

DOI：10.1124/mol.108.047985

Hydrogen sulfide (H(2)S) 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 H(2)S 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 H(2)S donor, concentration-dependently suppressed rotenone-induced cellular injury and apoptotic cell death. NaHS also prevented rotenone-induced p38- and c-Jun NH(2)-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 H(2)S inhibited rotenone-induced cell apoptosis via regulation of mitoK(ATP) channel/ p38- and JNK-MAPK pathway. Our data suggest that H(2)S may have potential therapeutic value for neurodegenerative diseases, such as PD.

• 出版日期2009-1