Inhibition of ROS-activated ERK1/2 pathway contributes to the protection of H2S against chemical hypoxia-induced injury in H9c2 cells
Inhibition of ROS-activated ERK1/2 pathway contributes to the protection of H2S against chemical hypoxia-induced injury in H9c2 cells
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DOI：
10.1007/s11010-011-1137-2
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发表时间：
2012-03-01
影响因子：
4.3
通讯作者：
Liao, Xin-Xue
中科院分区：
文献类型：
--
作者：
Dong, Xiao-Bian;Yang, Chun-Tao;Liao, Xin-Xue
硫化氢（H2S）已被证明具有心脏保护作用。然而，细胞外信号调节蛋白激酶1/2（ERK 1/2）在硫化氢诱导的心脏保护中的作用尚未完全阐明。本研究应用化学模拟缺氧剂氯化钴（CoCl 2）处理H9 c2细胞，建立化学缺氧诱导的心肌细胞损伤模型。结果表明，CoCl 2预处理H9 c2细胞后，NaHS（H2S供体）可降低H9 c2细胞活力，增加细胞凋亡率，降低线粒体膜电位（Delta Im），减少细胞内活性氧（ROS）的积累。H9 c2细胞暴露于CoCl 2或过氧化氢（H2 O2）可上调磷酸化（p）ERK 1/2的表达，而NaHS或N-乙酰基-L-半胱氨酸（ROS清除剂）预处理可降低磷酸化ERK 1/2的表达。更重要的是，ERK 1/2的选择性抑制剂U 0126模拟了H2S对CoCl 2诱导的H9 c2细胞损伤的上述细胞保护作用。总之，这些结果表明，H2S保护H9 c2细胞免受化学缺氧诱导的损伤，部分通过抑制ROS介导的ERK 1/2激活。
Hydrogen sulfide (H2S) has been shown to exert cardioprotective effects. However, the roles of extracellular signal-regulated protein kinases 1/2 (ERK1/2) in H2S-induced cardioprotection have not been completely elucidated. In this study, cobalt chloride (CoCl2), 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 H2S) before exposure to CoCl2 attenuated the decreased cell viability, the increased apoptosis rate, the loss of mitochondrial membrane potential (Delta Im), and the intracellular accumulation of reactive oxygen species (ROS) in H9c2 cells. Exposure of H9c2 cells to CoCl2 or hydrogen peroxide (H2O2) 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 H2S against CoCl2-induced injury in H9c2 cells. In conclusion, these results indicate that H2S protects H9c2 cells against chemical hypoxia-induced injury partially by inhibiting ROS-mediated activation of ERK1/2.