Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA.
Am J Physiol Regul Integr Comp Physiol. 2011 Feb;300(2):R236-50. doi: 10.1152/ajpregu.00230.2010. Epub 2010 Nov 10.
Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) or O-GlcNAcylation on serine and threonine residues of nuclear and cytoplasmic proteins is a posttranslational modification that alters the function of numerous proteins important in vascular function, including kinases, phosphatases, transcription factors, and cytoskeletal proteins. O-GlcNAcylation is an innovative way to think about vascular signaling events both in physiological conditions and in disease states. This posttranslational modification interferes with vascular processes, mainly vascular reactivity, in conditions where endothelin-1 (ET-1) levels are augmented (e.g. salt-sensitive hypertension, ischemia/reperfusion, and stroke). ET-1 plays a crucial role in the vascular function of most organ systems, both in physiological and pathophysiological conditions. Recognition of ET-1 by the ET(A) and ET(B) receptors activates intracellular signaling pathways and cascades that result in rapid and long-term alterations in vascular activity and function. Components of these ET-1-activated signaling pathways (e.g., mitogen-activated protein kinases, protein kinase C, RhoA/Rho kinase) are also targets for O-GlcNAcylation. Recent experimental evidence suggests that ET-1 directly activates O-GlcNAcylation, and this posttranslational modification mediates important vascular effects of the peptide. This review focuses on ET-1-activated signaling pathways that can be modified by O-GlcNAcylation. A brief description of the O-GlcNAcylation biology is presented, and its role on vascular function is addressed. ET-1-induced O-GlcNAcylation and its implications for vascular function are then discussed. Finally, the interplay between O-GlcNAcylation and O-phosphorylation is addressed.
O-连接β-N-乙酰葡萄糖胺（O-GlcNAc）糖基化或丝氨酸和苏氨酸残基上的 O-GlcNAc 化是一种翻译后修饰，可改变核质蛋白中许多对血管功能重要的蛋白质的功能，包括激酶、磷酸酶、转录因子和细胞骨架蛋白。O-GlcNAc 化是一种创新的思维方式，可以思考血管信号事件，无论是在生理条件下还是在疾病状态下。这种翻译后修饰会干扰血管过程，主要是血管反应性，在血管紧张素-1（ET-1）水平升高的情况下（例如盐敏感性高血压、缺血/再灌注和中风）。ET-1 在大多数器官系统的血管功能中都起着至关重要的作用，无论是在生理和病理生理条件下。ET-1 通过 ET(A)和 ET(B)受体识别，激活细胞内信号通路和级联反应，导致血管活性和功能的快速和长期改变。这些 ET-1 激活的信号通路的组成部分（例如，丝裂原活化蛋白激酶、蛋白激酶 C、RhoA/Rho 激酶）也是 O-GlcNAc 化的靶点。最近的实验证据表明，ET-1 可直接激活 O-GlcNAc 化，这种翻译后修饰介导肽的重要血管作用。本文综述了可被 O-GlcNAc 化修饰的 ET-1 激活的信号通路。简要介绍了 O-GlcNAc 化生物学，并讨论了其在血管功能中的作用。然后讨论了 ET-1 诱导的 O-GlcNAc 化及其对血管功能的影响。最后，探讨了 O-GlcNAc 化和 O-磷酸化之间的相互作用。
