title: Inhibition of ROS-activated ERK1/2 pathway contributes to the protection of H2S against chemical hypoxia-induced injury in H9c2 cells.
abstract: Hydrogen sulfide (H(2)S) has been shown to exert cardioprotective effects. However, the roles of extracellular signal-regulated protein kinases 1/2 (ERK1/2) in H(2)S-induced cardioprotection have not been completely elucidated. In this study, cobalt chloride (CoCl(2)), a chemical hypoxia mimetic agent, was applied to treat H9c2 cells to establish a chemical hypoxia-induced cardiomyocyte injury model. The results showed that pretreatment with NaHS (a donor of H(2)S) before exposure to CoCl(2) attenuated the decreased cell viability, the increased apoptosis rate, the loss of mitochondrial membrane potential (ΔΨm), and the intracellular accumulation of reactive oxygen species (ROS) in H9c2 cells. Exposure of H9c2 cells to CoCl(2) or hydrogen peroxide (H(2)O(2)) upregulated expression of phosphorylated (p) ERK1/2, which was reduced by pretreatment with NaHS or N-acetyl-L-cysteine, a ROS scavenger. More importantly, U0126, a selective inhibitor of ERK1/2, mimicked the above cytoprotection of H(2)S against CoCl(2)-induced injury in H9c2 cells. In conclusion, these results indicate that H(2)S protects H9c2 cells against chemical hypoxia-induced injury partially by inhibiting ROS-mediated activation of ERK1/2.
authors: Department of Cardiovasology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors: Xiao-Bian
authors: XB
authors: Dong
authors: Chun-Tao
authors: CT
authors: Yang
authors: Dong-Dan
authors: DD
authors: Zheng
authors: Li-Qiu
authors: LQ
authors: Mo
authors: Xiu-Yu
authors: XY
authors: Wang
authors: Ai-Ping
authors: AP
authors: Lan
authors: Fen
authors: F
authors: Hu
authors: Pei-Xi
authors: PX
authors: Chen
authors: Jian-Qiang
authors: JQ
authors: Feng
authors: Mei-Fen
authors: MF
authors: Zhang
authors: Xin-Xue
authors: XX
authors: Liao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D002070:Butadienes; D002316:Cardiotonic Agents; D009570:Nitriles; D017382:Reactive Oxygen Species; C113580:U 0126; D003035:Cobalt; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; C018021:cobaltous chloride; D006862:Hydrogen Sulfide