O-linked beta-N-acetylglucosamine during hyperglycemia exerts both anti-inflammatory and pro-oxidative properties in the endothelial system

• Published in: Oxidative medicine and cellular longevity 2009-07, Vol.2 (3), p.172-175
• Main Authors: Rajapakse, Angana Gupta, Ming, Xiu-Fen, Carvas, João M, Yang, Zhihong
• Format: Article
• Language: English
• Subjects: Acetylglucosamine - pharmacology; Anti-Inflammatory Agents - pharmacology; Cells, Cultured; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium, Vascular - cytology; Extra View; Hexosamines - biosynthesis; Humans; Hyperglycemia - metabolism; Intercellular Adhesion Molecule-1 - metabolism; Oxidants - pharmacology; Oxidative Stress; Tumor Necrosis Factor-alpha - metabolism; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 1942-0900; 1942-0994
• DOI: 10.4161/oxim.2.3.8482

Elevated cellular levels of protein O-linked beta-N-acetylglucosamine (O-GlcNAc) through hexosamine biosynthesis pathway (HBP) are suggested to contribute to cardiovascular adverse effects under chronic hyperglycemic condition associated with oxidative stress and inflammation. Conversely, enhancing O-GlcNAc levels have also been demonstrated being protective against myocardial ischemia/reperfusion injury. We recently demonstrated that hyperglycemia increases oxidative stress and HBP flux in endothelial cells and enhances endothelial expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in response to tumor necrosis factor-alpha (TNFalpha) through oxidative stress rather than HBP pathway. Here we present further complementary data showing that enhancing O-GlcNAc levels by glucosamine does not mimic hyperglycemia's effect on TNFalpha-induced endothelial VCAM-1 and ICAM-1 expression. Glucosamine however inhibits ICAM-1 (not VCAM-1) expression and induces superoxide generation in the cells. The results further suggest that increased O-GlcNAc levels do not mediate the enhancing effect of hyperglycemia on the endothelial inflammatory responses to TNFalpha. In contrast, it exerts certain anti-inflammatory effects accompanied by pro-oxidative properties. Further work should delineate the exact role of HPB pathway in different aspects of cardiovascular functions, especially those of diabetic cardiovascular complications.