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Role of O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins in diabetic cardiovascular complications.
Current Opinion in Pharmacology ( IF 4.0 ) Pub Date : 2020-09-13 , DOI: 10.1016/j.coph.2020.08.005
John C Chatham 1 , Martin E Young 2 , Jianhua Zhang 3
Affiliation  

The post-translational modification of serine and threonine residues of proteins by O-linked N-acetylglucosamine (O-GlcNAc) regulates diverse cellular processes in the cardiovascular system. UDP-GlcNAc is a substrate for O-GlcNAc transferase, which catalyzes the attachment of O-GlcNAc to proteins. O-GlcNAcase catalyzes the removal of O-GlcNAc from proteins. UDP-GlcNAc is the end product of the hexosamine biosynthesis pathway, which is regulated primarily by glucose-6-phosphate-Glutamine:fructose-6-phosphate amidotransferase (GFAT). GFAT catalyzes the formation of glucosamine-6-phosphate from fructose-6-phosphate and glutamine. Whereas O-GlcNAc is essential for cell viability, sustained increases in O-GlcNAc levels have been implicated in the etiology of many chronic diseases and is associated with glucose toxicity and diabetic complications in various organs including the cardiovascular system. This review provides an overview of the regulation of protein O-GlcNAcylation followed by a discussion of potential mechanisms by which dysregulation in O-GlcNAc cycling contributes to the adverse effects of diabetes on the cardiovascular system.



中文翻译:

O-连接的 N-乙酰氨基葡萄糖 (O-GlcNAc) 修饰蛋白质在糖尿病心血管并发症中的作用。

O-连接的 N-乙酰氨基葡萄糖 (O-GlcNAc) 对蛋白质丝氨酸和苏氨酸残基的翻译后修饰调节心血管系统中的多种细胞过程。UDP-GlcNAc 是 O-GlcNAc 转移酶的底物,可催化 O-GlcNAc 与蛋白质的结合。O-GlcNAcase 催化从蛋白质中去除 O-GlcNAc。UDP-GlcNAc 是己糖胺生物合成途径的最终产物,主要受 6-磷酸葡萄糖-谷氨酰胺:6-磷酸果糖氨基转移酶 (GFAT) 调节。GFAT 催化从 6-磷酸果糖和谷氨酰胺形成 6-磷酸葡萄糖胺。而 O-GlcNAc 对细胞活力至关重要,O-GlcNAc 水平的持续升高与许多慢性疾病的病因有关,并且与包括心血管系统在内的各种器官的葡萄糖毒性和糖尿病并发症有关。本综述概述了蛋白质 O-GlcNAc 化的调节,然后讨论了 O-GlcNAc 循环中的失调导致糖尿病对心血管系统的不利影响的潜在机制。

更新日期:2020-09-13
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