Molecular mechanisms underlying the activation of eNOS
Molecular mechanisms underlying the activation of eNOS
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DOI：
10.1007/s00424-009-0767-7
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发表时间：
2010-05-01
影响因子：
4.5
通讯作者：
Fleming, Ingrid
中科院分区：
文献类型：
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作者：
Fleming, Ingrid
位于血液和血管壁之间的界面处的内皮细胞在控制血管张力和稳态中起关键作用，特别是在决定促动脉粥样硬化基因和抗动脉粥样硬化基因的表达中。这些效应中的许多是由血管舒张剂一氧化氮（NO）的产生和释放的变化介导的，所述NO响应于由流动的血液（剪切应力）和血管壁的循环应变施加在内皮细胞的管腔表面上的血液动力学刺激。内皮NO合酶（eNOS）响应于流体剪切应力和多种激动剂经由细胞事件被激活，所述细胞事件例如：增加的细胞内Ca 2+、与底物和辅因子以及衔接子和调节蛋白的相互作用、蛋白磷酸化，以及通过在不同的亚细胞结构域之间穿梭。这些过程的失调导致eNOS活性减弱和NO输出减少，这是许多病理生理学病症如糖尿病和动脉粥样硬化的特征。本文综述了近年来有关eNOS活性调控的分子事件的研究进展。
Endothelial cells situated at the interface between blood and the vessel wall play a crucial role in controlling vascular tone and homeostasis, particularly in determining the expression of pro- and anti-atherosclerotic genes. Many of these effects are mediated by changes in the generation and release of the vasodilator nitric oxide (NO) in response to hemodynamic stimuli exerted on the luminal surface of endothelial cells by the streaming blood (shear stress) and the cyclic strain of the vascular wall. The endothelial NO synthase (eNOS) is activated in response to fluid shear stress and numerous agonists via cellular events such as; increased intracellular Ca2+, interaction with substrate and co-factors, as well as adaptor and regulatory proteins, protein phosphorylation, and through shuttling between distinct sub-cellular domains. Dysregulation of these processes leads to attenuated eNOS activity and reduced NO output which is a characteristic feature of numerous patho-physiological disorders such as diabetes and atherosclerosis. This review summarizes some of the recent findings relating to the molecular events regulating eNOS activity.