The roles ofO-linked β-N-acetylglucosamine in cardiovascular physiology and disease

Abstract

More than 1,000 proteins of the nucleus, cytoplasm, and mitochondria are dynamically modified by O-linked β- N-acetylglucosamine ( O-GlcNAc), an essential post-translational modification of metazoans. O-GlcNAc, which modifies Ser/Thr residues, is thought to regulate protein function in a manner analogous to protein phosphorylation and, on a subset of proteins, appears to have a reciprocal relationship with phosphorylation. Like phosphorylation, O-GlcNAc levels change dynamically in response to numerous signals including hyperglycemia and cellular injury. Recent data suggests that O-GlcNAc appears to be a key regulator of the cellular stress response, the augmentation of which is protective in models of acute vascular injury, trauma hemorrhage, and ischemia-reperfusion injury. In contrast to these studies, O-GlcNAc has also been implicated in the development of hypertension and type II diabetes, leading to vascular and cardiac dysfunction. Here we summarize the current understanding of the roles of O-GlcNAc in the heart and vasculature.

Nutrient-driven O-GlcNAc cycling – think globally but act locally

“…Both OGT and OGA are expressed in all tissue types, where they are necessary for either vertebrate development (OGT) or for the transition from the fetal stage to adulthood (OGA) (Shafi et al, 2000;Yang et al, 2012). Deregulation of O-GlcNAc cycling has been implicated in a variety of disease states, including cardiovascular disease, neurodegeneration, cancer and diabetes (Bond and Hanover, 2013;Hart et al, 2011;Ngoh et al, 2010;Zachara, 2012).…”

Update on innovative initiatives for the American Journal of Physiology-Heart and Circulatory Physiology

“…Among the many topics covered in this collection (24, 45, 88, 99, 112), we have published seminal articles on myocardial sheet therapy (31), gene and cytokine therapy for heart failure (65), cardiac regeneration therapy, and its connections to cardiac physiology (89), as well as nestinpositive cells and remodeling in cardiac disease states (13). The collection on "Post-translational Protein Modification in Metabolic Stress" contains articles on such topics as cardiac mitochondrial matrix and respiratory complex protein phosphorylation (20), post-translational regulation of peroxisome proliferator-activated receptor proteins by small ubiquitin-like modifier and ubiquitin (98), the role of sirtuin 3-mediated mitochondrial protein deacetylation in the heart (78), and O-linked ␤-N-acetylglucosamines in cardiac physiology (110).…”

O-Linked β-N-Acetylglucosamine (O-GlcNAc) Regulates Emerin Binding to Barrier to Autointegration Factor (BAF) in a Chromatin- and Lamin B-enriched “Niche”

“…Emerin also has features (rich in Ser/Thr residues; large regions of predicted disorder) characteristic of proteins modified by O-linked ␤-Nacetylglucosamine (O-GlcNAc) (46 -48), a single sugar modification of Ser or Thr residues that is abundant, reversible, and dynamic. O-GlcNAcylated proteins are found in the cytoplasm, mitochondria, and nucleus (49), especially the nuclear envelope (50,51). O-GlcNAc modification can compete or augment phosphorylation to regulate signaling, transcription, mitosis, and stress responses (52).…”