The pro-oxidant role of methylglyoxal in mesenteric artery smooth muscle cells.
Methylglyoxal (MG), a highly reactive metabolite of glucose, causes non-enzymatic glycation of proteins to form irreversible advanced glycation endproducts (AGEs). The present study investigated whether methylglyoxal induced oxidative stress and activated nuclear factor kappa B (NF-kappaB) in freshly isolated and cultured smooth muscle cells (SMCs) from rat mesenteric artery. The treatment of cells with MG (50 or 100 micromol/L) induced a significant increase in AGE formation and oxidation of DCF. MG-enhanced generation of AGEs and the oxidation of DCF was markedly inhibited by antioxidant n-acetylcysteine (NAC, 600 micromol/L). MG at a concentration of 100 micromol/L increased the heme-oxygenase-1 expression in these cells. Moreover, MG activated NF-kappaB p65, indicated by an increased immuno cytochemistry stain for NF-kappaB p65 located in the nucleus after the treatment of mesenteric artery SMCs with MG. MG-induced activation of NF-kappaB p65 was inhibited by NAC. In summary, MG significantly increases oxidative stress and activates NF-kappaB p65 in mesenteric artery SMCs. The pro-oxidant role of methylglyoxal may contribute to various pathological changes of SMCs from resistance arteries.
Wu
Lingyun
L
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada. liw070@duke.usask.ca
D000818:Animals; D002478:Cells, Cultured; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011765:Pyruvaldehyde / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D011765:Pyruvaldehyde; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1