Mechanisms involved in the contraction of endothelial cells by hydrogen peroxide
Mechanisms involved in the contraction of endothelial cells by hydrogen peroxide
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DOI：
10.1016/s0891-5849(98)00223-8
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发表时间：
1999-03-01
影响因子：
7.4
通讯作者：
Rodríguez-Puyol, D
中科院分区：
文献类型：
--
作者：
López-Ongil, S;Torrecillas, G;Rodríguez-Puyol, D
内皮细胞收缩在炎性水肿发生中的重要性已被报道。ROS是在病理条件下合成的代谢物，在病理条件下发生了显著的血管内液体泄漏，如缺血-再灌注。本实验旨在验证ROS，特别是H2O2可能引起内皮细胞收缩的假设，并探讨其相关机制。H2O2培养的牛主动脉内皮细胞显示平面细胞表面积（PCSA）显著降低，肌球蛋白轻链磷酸化（MLCP）显著增加，且具有时间和剂量依赖性，无明显毒性。sulotroban （TxA(2)拮抗剂）或bn52021 （PAF拮抗剂）不会阻断H2O2的这种作用。氯化镧（钙通道阻滞剂）和EGTA部分抑制H2O2诱导的MLCP升高。H7和staurosporine， PKC抑制剂和PKC下调（肉豆酸酯phorbol acetate处理，24 h）也阻断h2o2依赖性内皮细胞收缩，以PCSA或MLCP测量。H2O2增加了细胞内钙浓度，EGTA和氯化镧减弱了这一作用。H2O2还增加了一个80 kD多肽的磷酸化，可能是PKC底物MARCKS。总之，目前的结果表明内皮细胞的ros依赖性收缩，这一效应可以解释在某些病理生理情况下观察到的血管内液体泄漏。钙和PKC可能参与了这种收缩的发展。(C) 1999 Elsevier Science Inc.；
The importance of endothelial contraction in the genesis of inflammatory edema has been reported. ROS are metabolites synthesized in pathological conditions in that a significant intravascular fluid leak occurs, such as ischemia-reperfusion. Present experiments were designed to test the hypothesis that ROS, particularly H2O2, may elicit the contraction of endothelial cells, and to explore the mechanisms involved. Bovine aortic endothelial cells incubated with H2O2 showed a significant reduction in planar cell surface area (PCSA), and a significant increase in myosin light chain phosphorylation (MLCP), with a time- and dose-dependent pattern, without any significant toxicity. This effect of H2O2 was not blocked by sulotroban (TxA(2) antagonist) or BN 52021 (PAF antagonist). Lanthanum chloride (calcium channel blocker) and EGTA partially inhibited the increase in MLCP induced by H2O2. H7 and staurosporine, PKC inhibitors, and PKC down-regulation (phorbol myristate acetate treatment, 24 h) also blocked H2O2-dependent endothelial contraction, measured as PCSA or MLCP. H2O2 increased the intracellular calcium concentration, an effect blunted by EGTA and lanthanum chloride. H2O2 also increased the phosphorylation of an 80 kD polypeptide, probably MARCKS, a PKC substrate. In summary, the present results demonstrate the ROS-dependent contraction of endothelial cells, an effect that could explain the intravascular fluid leak observed in some pathophysiological situations. Calcium and PKC may be involved in the development of this contraction. (C) 1999 Elsevier Science Inc.