Angana Gupta Rajapakse, Xiu-Fen Ming, João M. Carvas, Zhihong Yang, "O-linked β-N-acetylglucosamine During Hyperglycemia Exerts Both Anti-Inflammatory and Pro-Oxidative Properties in the Endothelial System", Oxidative Medicine and Cellular Longevity, vol. 2, Article ID 435808, 4 pages, 2009. https://doi.org/10.4161/oxim.2.3.8482
O-linked β-N-acetylglucosamine During Hyperglycemia Exerts Both Anti-Inflammatory and Pro-Oxidative Properties in the Endothelial System
Elevated cellular levels of protein O-linked β-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-α (TNFα) 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 TNFα-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 TNFα. 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.
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