title: Hydrogen sulfide prevents OGD/R-induced apoptosis by suppressing the phosphorylation of p38 and secretion of IL-6 in PC12 cells.
abstract: Hydrogen sulfide (H2S), a well-known endogenous mediator, has been shown to exert protective effects against neuronal damage caused by brain ischemia, but the mechanism of its action remains unclear. We have reported the neuroprotective properties of H2S against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury by inhibiting the phosphorylation of p38. The present study evaluates the effect of H2S on OGD/R-induced cell injury or apoptosis and the mechanisms for its action in PC12 cells. Pretreatment of PC12 cells with exogenous sodium hydrosulfide (NaHS) (a H2S donor, 100 or 300 µM) for 12 h before exposure to OGD/R markedly attenuated p38 phosphorylation. Activation of p38 MAPK by transfection of activated p38α, but not p38β, reversed the protective effect of NaHS, as measured by enzyme-linked immunosorbent assay analysis. Importantly, SB203580 (a p38 MAPK inhibitor) also reversed the protective effects of p38α-activated p38 MAPK. Interleukin-6 secretion after OGD/R decreased significantly with NaHS compared with without NaHS. Taken together, we show that the p38 pathway contributes toward OGD/R-induced cell death and p38α plays a key role in OGD/R-induced interleukin-6 secretion.
authors.affiliation: Department of Neurology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Tang
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Hou
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.forename: Chaochao
authors.initials: C
authors.lastname: Gu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000172:deficiency*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D018696:Neuroprotective Agents; D007770:L-Lactate Dehydrogenase; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D006862:Hydrogen Sulfide