Cytoskeletal changes in hypoxic pulmonary endothelial cells are dependent on MAPK-activated protein kinase MK2
Cytoskeletal changes in hypoxic pulmonary endothelial cells are dependent on MAPK-activated protein kinase MK2
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DOI：
10.1074/jbc.m205863200
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发表时间：
2002-11-08
影响因子：
4.8
通讯作者：
Hassoun, PM
中科院分区：
文献类型：
--
作者：
Kayyali, US;Pennella, CM;Hassoun, PM
暴露于缺氧引起内皮细胞层的结构变化，改变其渗透性及其与白细胞和血小板的相互作用。细胞骨架对应激反应的一个特征性变化是肌动蛋白细胞骨架的重组和应力纤维的形成。本文介绍了缺氧时肺微血管内皮细胞骨架的变化及其可能的机制。低氧诱导的肌动蛋白再分布似乎是由MAPK p38下游的组分介导的，MAPK p38在肺内皮细胞中响应于低氧而被激活。我们的研究结果表明，激酶MM，这是一个底物的p38，成为激活缺氧，导致磷酸化的底物之一，HSP 27。由于已知HSP 27磷酸化会改变肌动蛋白在其他刺激下的分布，我们推测它也会导致缺氧时观察到的肌动蛋白重新分布。这一观点得到了以下观察结果的支持，即在过度表达组成型活性MK 2或磷酸模拟HSP 27突变体的细胞中发生了类似的肌动蛋白再分布。过表达显性负性MK2阻断缺氧对肌动蛋白细胞骨架的影响。总之，这些结果表明，缺氧刺激p38-MK 2-HSP 27途径，导致肌动蛋白细胞骨架的显着改变。
Exposure to hypoxia causes structural changes in the endothelial cell layer that alter its permeability and its interaction with leukocytes and platelets. One of the well characterized cytoskeletal changes in response to stress involves the reorganization of the actin cytoskeleton and the formation of stress fibers. This report describes cytoskeletal changes in pulmonary microvascular endothelial cells in response to hypoxia and potential mechanisms involved in this process. The hypoxia-induced actin redistribution appears to be mediated by components downstream of MAPK p38, which is activated in pulmonary endothelial cells in response to hypoxia. Our results indicate that kinase MM, which is a substrate of p38, becomes activated by hypoxia, leading to the phosphorylation of one of its substrates, HSP27. Because HSP27 phosphorylation is known to alter actin distribution in response to other stimuli, we postulate that it also causes the actin redistribution observed in hypoxia. This notion is supported by the observations that similar actin redistribution occurs in cells overexpressing constitutively active MK2 or phosphomimicking HSP27 mutant. Overexpressing dominant negative MK2 blocks the effects of hypoxia on the actin cytoskeleton. Taken together these results indicate that hypoxia stimulates the p38-MK2-HSP27 pathway leading to significant alteration in the actin cytoskeleton.