title: O-GlcNAc signaling in the cardiovascular system.
abstract: Cardiovascular function is regulated at multiple levels. Some of the most important aspects of such regulation involve alterations in an ever-growing list of posttranslational modifications. One such modification orchestrates input from numerous metabolic cues to modify proteins and alter their localization and/or function. Known as the beta-O-linkage of N-acetylglucosamine (ie, O-GlcNAc) to cellular proteins, this unique monosaccharide is involved in a diverse array of physiological and pathological functions. This review introduces readers to the general concepts related to O-GlcNAc, the regulation of this modification, and its role in primary pathophysiology. Much of the existing literature regarding the role of O-GlcNAcylation in disease addresses the protracted elevations in O-GlcNAcylation observed during diabetes. In this review, we focus on the emerging evidence of its involvement in the cardiovascular system. In particular, we highlight evidence of protein O-GlcNAcylation as an autoprotective alarm or stress response. We discuss recent literature supporting the idea that promoting O-GlcNAcylation improves cell survival during acute stress (eg, hypoxia, ischemia, oxidative stress), whereas limiting O-GlcNAcylation exacerbates cell damage in similar models. In addition to addressing the potential mechanisms of O-GlcNAc-mediated cardioprotection, we discuss technical issues related to studying protein O-GlcNAcylation in biological systems. The reader should gain an understanding of what protein O-GlcNAcylation is and that its roles in the acute and chronic disease settings appear distinct.
authors.affiliation: Institute of Molecular Cardiology, University of Louisville, 580 South Preston St, 404C, Baxter II-404C, Louisville, KY 40202, USA.
authors.forename: Gladys A
authors.initials: GA
authors.lastname: Ngoh
authors.forename: Heberty T
authors.initials: HT
authors.lastname: Facundo
authors.forename: Ayesha
authors.initials: A
authors.lastname: Zafir
authors.forename: Steven P
authors.initials: SP
authors.lastname: Jones
mesh_terms: D000117:Acetylglucosamine / Q000235:genetics / Q000378:metabolism*; D000215:Acylation; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology; D002319:Cardiovascular System / Q000378:metabolism* / Q000503:physiopathology; D002453:Cell Cycle; D002470:Cell Survival; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology; D006031:Glycosylation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological; D014158:Transcription, Genetic
chemical_list: D007328:Insulin; D000117:Acetylglucosamine