Lima Victor V, Rigsby Christiné S, Hardy David M, Webb R Clinton, Tostes Rita C
Department of Physiology, Medical College of Georgia, Augusta, GA, USA; Department of Pharmacology, University of Sao Paulo, Sao Paulo, SP, Brazil.
J Am Soc Hypertens. 2009 Nov-Dec;3(6):374-87. doi: 10.1016/j.jash.2009.09.004.
O-Linked attachment of beta-N-acetyl-glucosamine (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins is a highly dynamic posttranslational modification that plays a key role in signal transduction pathways. Preliminary data show that O-GlcNAcylation may represent a key regulatory mechanism in the vasculature, modulating contractile and relaxant responses. Proteins with an important role in vascular function, such as endothelial nitric oxide synthase, sarcoplasmic reticulum Ca(2+)-ATPase, protein kinase C, mitogen-activated protein kinases, and proteins involved in cytoskeleton regulation and microtubule assembly are targets for O-GlcNAcylation, indicating that this posttranslational modification may play an important role in vascular reactivity. Here, we will focus on a few specific pathways that contribute to vascular function and cardiovascular disease-associated vascular dysfunction, and the implications of their modification by O-GlcNAc. New chemical tools have been developed to detect and study O-GlcNAcylation, including inhibitors of O-GlcNAc enzymes, chemoenzymatic tagging methods, and quantitative proteomics strategies; these will also be briefly addressed. An exciting challenge in the future will be to better understand the cellular dynamics of this posttranslational modification, as well as the signaling pathways and mechanisms by which O-GlcNAc is regulated on specific proteins in the vasculature in health and disease.
β-N-乙酰葡糖胺（O-GlcNAc）与核蛋白和胞质蛋白的丝氨酸和苏氨酸残基的O-连接附着是一种高度动态的翻译后修饰，在信号转导途径中起关键作用。初步数据表明，O-GlcNAc糖基化可能代表血管系统中的一种关键调节机制，调节收缩和舒张反应。在血管功能中起重要作用的蛋白质，如内皮型一氧化氮合酶、肌浆网Ca(2+)-ATP酶、蛋白激酶C、丝裂原活化蛋白激酶以及参与细胞骨架调节和微管组装的蛋白质，都是O-GlcNAc糖基化的靶点，这表明这种翻译后修饰可能在血管反应性中起重要作用。在这里，我们将重点关注一些有助于血管功能和心血管疾病相关血管功能障碍的特定途径，以及它们被O-GlcNAc修饰的意义。已经开发出了新的化学工具来检测和研究O-GlcNAc糖基化，包括O-GlcNAc酶抑制剂、化学酶标记方法和定量蛋白质组学策略；这些也将简要介绍。未来一个令人兴奋的挑战将是更好地理解这种翻译后修饰的细胞动力学，以及在健康和疾病状态下，血管系统中特定蛋白质上O-GlcNAc的调节信号通路和机制。
