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-κB) in freshly isolated and cultured smooth muscle cells (SMCs) from rat mesenteric artery. The treatment of cells with MG (50 or 100 µmol/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 µmol/L). MG at a concentration of 100 µmol/L increased the heme-oxygenase-1 expression in these cells. Moreover, MG activated NF-κB p65, indicated by an increased im muno cytochemistry stain for NF-κB p65 located in the nucleus after the treatment of mesenteric artery SMCs with MG. MG-induced activation of NF-κB p65 was inhibited by NAC. In summary, MG significantly increases oxidative stress and activates NF-κB p65 in mesenteric artery SMCs. The pro-oxidant role of methylglyoxal may contribute to various pathological changes of SMCs from resistance arteries.Key words: methylglyoxal, oxidative stress, NF-κB p65, vascular smooth muscle cells, mesenteric artery.