O-GlcNAc Signaling in the Cardiovascular System

• Published in: Circulation research Vol. 107; no. 2; pp. 171 - 185
• Main Authors: Ngoh, Gladys A, Facundo, Heberty T, Zafir, Ayesha, Jones, Steven P
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 23-07-2010; Lippincott Williams & Wilkins
• Subjects: Acetylglucosamine - genetics; Acetylglucosamine - metabolism; Acylation; Animals; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - physiopathology; Cardiovascular System - metabolism; Cardiovascular System - physiopathology; Cell Cycle; Cell Survival; Coronary heart disease; Diabetes Mellitus - metabolism; Diabetes Mellitus - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fundamental and applied biological sciences. Psychology; Glycosylation; Heart; Humans; Insulin - metabolism; Medical sciences; Myocytes, Cardiac - metabolism; Phosphorylation; Protein Processing, Post-Translational; Signal Transduction - genetics; Stress, Physiological; Transcription, Genetic; Vertebrates: cardiovascular system; Endocrinopathy; Diabetes mellitus; Cardiovascular disease; Myocardial ischemia; Glucose; Coronary heart disease; Myocardial disease; Vascular disease; Signal transduction; Vertebrata; Mitochondria; Mammalia; Circulatory system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.110.224675

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 β-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.