Copyright © 2006, European Society of Cardiology
Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system
aDepartment of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama, United States
bDepartment of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States
* Corresponding author. University of Alabama at Birmingham, Department of Medicine, 1530 3rd Avenue South, MCLM 684, Birmingham, AL 35294-0005, United States. Tel.: +1 205 934 0240; fax: +1 205 934 0950. Email address: jchatham{at}uab.edu
There is growing recognition that the O-linked attachment of N-acetyl-glucosamine (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins is a highly dynamic post-translational modification that plays a key role in signal transduction pathways. Numerous proteins have been identified as targets of O-GlcNAc modifications including kinases, phosphatases, transcription factors, metabolic enzymes, chaperons, and cytoskeletal proteins. Modulation of O-GlcNAc levels has been shown to modify DNA binding, enzyme activity, protein–protein interactions, the half-life of proteins, and subcellular localization. The level of O-GlcNAc is regulated in part by the metabolism of glucose via the hexosamine biosynthesis pathway (HBP), and the metabolic abnormalities associated with insulin resistance and diabetes, such as hyperglycemia, hyperlipidemia, and hyperinsulinemia, are all associated with increased flux through the HBP and elevated O-GlcNAc levels. Increased HBP flux and O-GlcNAc levels have been implicated in the impaired relaxation of isolated cardiomyocytes, blunted response to angiotensin II and phenylephrine, hyperglycemia-induced cardiomyocyte apoptosis, and endothelial and vascular cell dysfunction. In contrast to these adverse effects, recent studies have also shown that O-GlcNAc levels increase in response to acute stress and that this is associated with increased cell survival. Thus, while the relationship between O-GlcNAc levels and cellular function is complex and not well-understood, it is clear that these pathways play a critical role in the regulation of cell function and survival in the cardiovascular system and may be implicated in the adverse effects of metabolic disease on the heart.
KEYWORDS Hexosamine biosynthesis; Protein O-glycosylation; O-GlcNAc transferase; Diabetes
Time for primary review 21 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. J. Chess and W. C. Stanley Role of diet and fuel overabundance in the development and progression of heart failure Cardiovasc Res, July 15, 2008; 79(2): 269 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Champattanachai, R. B. Marchase, and J. C. Chatham Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein O-GlcNAc and increased mitochondrial Bcl-2 Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1509 - C1520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Rask-Madsen and G. L. King More Sugar, Less Blood Vessels: Another Piece in the Puzzle of Increased Cardiovascular Risk in Diabetes Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 608 - 610. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhou, Y. Wei, D. Liu, X. Ge, F. Zhou, X. Yun, J. Jiang, and J. Gu Identification of {beta}1,4GalT II as a Target Gene of p53-mediated HeLa Cell Apoptosis J. Biochem., April 1, 2008; 143(4): 547 - 554. [Abstract] [Full Text] [PDF]
|
|