title: Post-translational protein modification by O-linked N-acetyl-glucosamine: its role in mediating the adverse effects of diabetes on the heart.
abstract: 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.
authors.affiliation: Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McLarty
authors.forename: Susan A
authors.initials: SA
authors.lastname: Marsh
authors.forename: John C
authors.initials: JC
authors.lastname: Chatham
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism*; D058065:Diabetic Cardiomyopathies / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance; D008954:Models, Biological; D011499:Protein Processing, Post-Translational / Q000502:physiology
chemical_list: D000117:Acetylglucosamine