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

Abstract

Hydrogen sulfide (H 2 S) 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 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 humanderived 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 (⌬⌿ 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.

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

“…Additionally, exogenous H 2 S reduces doxorubicin-induced cardiotoxicity by inhibiting the activation of the p38 MAPK pathway (29). Our results, as well as those from previous studies (22,29,40,41) suggest that exogenous H 2 S may be a potential inhibitor of p38 MAPK.…”

“…The involvement of hte inhibition of the p38 MAPK pathway in the cytoprotective effects of exogenous H 2 S has also been reported by other studies. Hu et al indicated that H 2 S suppresses LPS-induced inflammation by inhibiting p38 MAPK in microglia (40) and that H 2 S protects SH-SY5Y cells against rotenone-induced apoptosis through the suppression of p38 MAPK activation (41). Additionally, exogenous H 2 S reduces doxorubicin-induced cardiotoxicity by inhibiting the activation of the p38 MAPK pathway (29).…”

Hydrogen sulfide treatment improves long-term renal dysfunction resulting from prolonged warm renal ischemia-reperfusion injury

“…Multiple studies have demonstrated that H 2 S is capable of limiting leukocyte migration, and cytokine expression and release. [22][23][24][30][31][32] We found that H 2 S treatment during warm IRI initially decreased the expression of pro-inflammatory markers, increased the expression of pro-survival marker Bcl-2 and decreased the expression of pro-apoptotic marker BID. While the expression of these markers decreased toward Hydrogen sulfide treatment and long-term renal dysfunction baseline by day 7, H 2 S treatment also resulted in decreased long-term renal inflammation as evidenced by the diminished numbers of infiltrating macrophages in H 2 S treated kidneys at day 7.…”

Hydrogen sulfide inhibits homocysteine-induced endoplasmic reticulum stress and neuronal apoptosis in rat hippocampus via upregulation of the BDNF-TrkB pathway

“…Therefore, we have previously explored if H 2 S directly antagonizes the toxicity of Hcy to neuronal cells, and our previous data revealed that H 2 S could attenuate the neurotoxicity of Hcy [31] . It has been reported that H 2 S serves as a protective gaseous signaling molecule in the nervous system by preserving mitochondrial function [50,51] . The ER is another important subcellular organelle critical for protein folding and the formation of disulfide bonds [52] .…”