Cyclooxygenase-2 mediates hydrogen peroxide-induced wound repair in human endothelial cells
Cyclooxygenase-2 mediates hydrogen peroxide-induced wound repair in human endothelial cells
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DOI：
10.1016/j.freeradbiomed.2009.02.026
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发表时间：
2009-05-15
影响因子：
7.4
通讯作者：
Colli, Susanna
中科院分区：
文献类型：
--
作者：
Eligini, Sonia;Arenaz, Izaskun;Colli, Susanna
由内皮细胞产生的环氧合酶-2（考克斯-2）代谢物，特别是前列环素和前列腺素E-2，深刻地影响血管张力、局部血流和血管生成。我们以前已经表明，活性氧诱导考克斯-2在人内皮细胞（HUVEC）的表达，无论是对自己的或作为组件的信号通路触发的TNF α，原型炎症细胞因子。在此，我们研究了过氧化氢（H2 O2）诱导的考克斯-2的作用，无论是外源性或内源性产生的TNF α，在修复的机械损伤的HUVEC单层和探测的H2 O2的来源，参与TNF α信号和途径，通过H2 O2调节考克斯-2的表达。结果表明，H2 O2诱导的考克斯-2活性参与损伤的单层细胞的修复。NADPH氧化酶和线粒体电子传递链都参与H2 O2的产生。H2 O2引发的考克斯-2诱导信号通过增加蛋白磷酸酶活性抑制后的蛋白酪氨酸激酶磷酸化而起作用。p38 MAPK的激活及其在抑制丝氨酸/苏氨酸磷酸酶活性中的相互作用是该事件中的关键步骤。结论：H2 O2诱导的考克斯-2在促进内皮损伤后的修复中起重要作用，因此考克斯-2的心脏保护作用至少部分是由于其修复受损内皮的能力。(C)2009 Elsevier Inc. All rights reserved.
Cyclooxygenase-2 (Cox-2) metabolites produced by endothelial cells, particularly prostacyclin and prostaglandin E-2, profoundly affect vascular tone, regional blood flow, and angiogenesis. We have previously shown that reactive oxygen species induce Cox-2 expression in human endothelial cells (HUVEC), either on their own or as components of the signaling pathway triggered by TNF alpha, the prototypical inflammatory cytokine. Here we investigated the role of Cox-2 induced by hydrogen peroxide (H2O2), either exogenous or endogenously generated by TNFa, in the repair of a mechanically wounded HUVEC monolayer and probed the sources of H2O2 that are involved in TNFa signaling and the pathways through which H2O2 modulates Cox-2 expression. Results indicate that H2O2-induced Cox-2 activity participates in the repair of wounded monolayers. Both NADPH oxidase and the mitochondrial electron transport chain are involved in H2O2 generation. Signaling triggered by H2O2 for Cox-2 induction acts by increasing the protein tyrosine kinase phosphorylation that follows inhibition of protein phosphatase activity. The activation of p38 MAPK and its interaction in the inhibition of serine/threonine phosphatase activity are both critical steps in this event. We conclude that Cox-2 induced by H2O2 plays an important role in promoting endothelial wound repair after injury, so that the cardioprotective effect of Cox-2 is due at least in part to its power of healing damaged endothelium. (C) 2009 Elsevier Inc. All rights reserved.