title: Protein O-GlcNAcylation: a new signaling paradigm for the cardiovascular system.
abstract: The posttranslational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide beta-N-acetylglucosamine (O-GlcNAc) is a highly dynamic and ubiquitous protein modification. Protein O-GlcNAcylation is rapidly emerging as a key regulator of critical biological processes including nuclear transport, translation and transcription, signal transduction, cytoskeletal reorganization, proteasomal degradation, and apoptosis. Increased levels of O-GlcNAc have been implicated as a pathogenic contributor to glucose toxicity and insulin resistance, which are both major hallmarks of diabetes mellitus and diabetes-related cardiovascular complications. Conversely, there is a growing body of data demonstrating that the acute activation of O-GlcNAc levels is an endogenous stress response designed to enhance cell survival. Reports on the effect of altered O-GlcNAc levels on the heart and cardiovascular system have been growing rapidly over the past few years and have implicated a role for O-GlcNAc in contributing to the adverse effects of diabetes on cardiovascular function as well as mediating the response to ischemic injury. Here, we summarize our present understanding of protein O-GlcNAcylation and its effect on the regulation of cardiovascular function. We examine the pathways regulating protein O-GlcNAcylation and discuss, in more detail, our understanding of the role of O-GlcNAc in both mediating the adverse effects of diabetes as well as its role in mediating cellular protective mechanisms in the cardiovascular system. In addition, we also explore the parallels between O-GlcNAc signaling and redox signaling, as an alternative paradigm for understanding the role of O-GlcNAcylation in regulating cell function.
authors.affiliation: Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-0007, USA.
authors.forename: Boglarka
authors.initials: B
authors.lastname: Laczy
authors.forename: Bradford G
authors.initials: BG
authors.lastname: Hill
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Paterson
authors.forename: C Roger
authors.initials: CR
authors.lastname: White
authors.forename: Dongqi
authors.initials: D
authors.lastname: Xing
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Chen
authors.forename: Victor
authors.initials: V
authors.lastname: Darley-Usmar
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.forename: John C
authors.initials: JC
authors.lastname: Chatham
mesh_terms: D000117:Acetylglucosamine / Q000502:physiology*; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D006031:Glycosylation; D006801:Humans; D032383:Myocytes, Cardiac / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000502:physiology
chemical_list: D042461:Vascular Endothelial Growth Factor A; D000117:Acetylglucosamine