Department of Obstetrics and Gynaecology, University of Texas Medical Branch, Galveston, TX, USA.
Clin Exp Pharmacol Physiol. 2013 Nov;40(11):753-64. doi: 10.1111/1440-1681.12136.
Complex regulatory processes alter the activity of endothelial nitric oxide synthase (eNOS) leading to nitric oxide (NO) production by endothelial cells under various physiological states. These complex processes require specific subcellular eNOS partitioning between plasma membrane caveolar domains and non-caveolar compartments. Translocation of eNOS from the plasma membrane to intracellular compartments is important for eNOS activation and subsequent NO biosynthesis. We present data reviewing and interpreting information regarding: (i) the coupling of endothelial plasma membrane receptor systems in the caveolar structure relative to eNOS trafficking; (ii) how eNOS trafficking relates to specific protein-protein interactions for inactivation and activation of eNOS; and (iii) how these complex mechanisms confer specific subcellular location relative to eNOS multisite phosphorylation and signalling. Dysfunction in the regulation of eNOS activation may contribute to several disease states, in particular gestational endothelial abnormalities (pre-eclampsia, gestational diabetes etc.), that have life-long deleterious health consequences that predispose the offspring to develop hypertensive disease, Type 2 diabetes and adiposity.
复杂的调控过程改变了内皮型一氧化氮合酶（eNOS）的活性，导致内皮细胞在各种生理状态下产生一氧化氮（NO）。这些复杂的过程需要特定的亚细胞 eNOS 在质膜小窝域和非小窝隔室之间进行分区。eNOS 从质膜向细胞内隔室的易位对于 eNOS 的激活和随后的 NO 生物合成很重要。我们提供的数据回顾和解释了以下信息：（i）内皮质膜受体系统与 eNOS 运输在小窝结构中的偶联；（ii）eNOS 运输与 eNOS 失活和激活的特定蛋白-蛋白相互作用的关系；以及（iii）这些复杂的机制相对于 eNOS 多部位磷酸化和信号转导赋予了特定的亚细胞定位。eNOS 激活的调节功能障碍可能导致多种疾病状态，特别是妊娠期内皮异常（子痫前期、妊娠期糖尿病等），这些疾病状态会对健康造成终身的不良影响，使后代易患高血压、2 型糖尿病和肥胖症。
