Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Life Sci. 2013 Mar 28;92(11):621-7. doi: 10.1016/j.lfs.2012.08.006. Epub 2012 Aug 11.
The post-translation attachment of O-linked N-acetylglucosamine, or O-GlcNAc, to serine and threonine residues of nuclear and cytoplasmic proteins is increasingly recognized as a key regulator of diverse cellular processes. O-GlcNAc synthesis is essential for cell survival and it has been shown that acute activation of pathways, which increase cellular O-GlcNAc levels is cytoprotective; however, prolonged increases in O-GlcNAcylation have been implicated in a number of chronic diseases. Glucose metabolism via the hexosamine biosynthesis pathway plays a central role in regulating O-GlcNAc synthesis; consequently, sustained increases in O-GlcNAc levels have been implicated in glucose toxicity and insulin resistance. Studies on the role of O-GlcNAc in regulating cardiomyocyte function have grown rapidly over the past decade and there is growing evidence that increased O-GlcNAc levels contribute to the adverse effects of diabetes on the heart, including impaired contractility, calcium handling, and abnormal stress responses. Recent evidence also suggests that O-GlcNAc plays a role in epigenetic control of gene transcription. The goal of this review is to provide an overview of our current knowledge about the regulation of protein O-GlcNAcylation and to explore in more detail O-GlcNAc-mediated responses in the diabetic heart.
O-连接的 N-乙酰葡萄糖胺（O-GlcNAc）的翻译后附着到核和细胞质蛋白的丝氨酸和苏氨酸残基上，越来越被认为是调节多种细胞过程的关键调节剂。O-GlcNAc 的合成对于细胞存活至关重要，已经表明，急性激活可增加细胞 O-GlcNAc 水平的途径具有细胞保护作用；然而，O-GlcNAcylation 的延长增加与许多慢性疾病有关。通过己糖胺生物合成途径的葡萄糖代谢在调节 O-GlcNAc 合成中起着核心作用；因此，O-GlcNAc 水平的持续升高与葡萄糖毒性和胰岛素抵抗有关。在过去十年中，关于 O-GlcNAc 调节心肌细胞功能的研究迅速增加，越来越多的证据表明，O-GlcNAc 水平的升高导致糖尿病对心脏的不良影响，包括收缩性、钙处理和异常应激反应受损。最近的证据还表明，O-GlcNAc 在基因转录的表观遗传控制中发挥作用。这篇综述的目的是提供对蛋白质 O-GlcNAc 化调节的当前知识的概述，并更详细地探讨糖尿病心脏中的 O-GlcNAc 介导的反应。
