期刊
LIFE SCIENCES
卷 92, 期 11, 页码 621-627出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2012.08.006
关键词
O-GlcNAc; O-GlcNAcylation; Diabetes; Cardiomyocytes
资金
- National Heart, Lung, and Blood Institute [HL104549, HL101192, HL079364]
- Washington State University Office of Research
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. (c) 2012 Elsevier Inc. All rights reserved.
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