Turkseven S.Ertuna E.Yetik-Anacak G.Yasa M.2019-10-262019-10-2620140792-6855https://doi.org/10.1515/jbcpp-2013-0095https://hdl.handle.net/11454/17617Background: Methylglyoxal is a major precursor in the formation of advanced glycation end products and is associated with the pathogenesis of diabetes-related vascular complications. The aim of this study was to evaluate whether methylglyoxal induces endothelial dysfunction and to determine the contributors involved in this process. Methods: Rat thoracic aortic rings were treated for 24 h with 100 µM methylglyoxal by using an organ culture method. A cumulative dose-response curve to acetylcholine was obtained to determine endothelium-dependent relaxation. The protein levels of endothelial nitric oxide synthase (eNOS) and its phosphorylated form at the serine 1177 site [p-eNOS (Ser1177)], heat shock protein 90 (Hsp90), AMP-activated protein kinase (AMPK?) and its phosphorylated form at the threonine 172 site [p-AMPK? (Thr172)] were evaluated. Superoxide production was determined by lucigenin-chemiluminescence. Results: Treatment with 100 µM methylglyoxal for 24 h decreased acetylcholine-induced vascular relaxation. The levels of eNOS and p-eNOS (Ser1177) were reduced while no effect on Hsp90 was observed. Levels of p-AMPK? (Thr172) were significantly decreased without any change in total AMPK? protein levels. Superoxide level was not affected by methylglyoxal treatment. Conclusions: In rat aortic rings, methylglyoxal determines a reduction in endothelium-dependent relaxation. This effect seems to be mediated via a reduction in p-eNOS (Ser1177) and p-AMPK(Thr172).en10.1515/jbcpp-2013-0095info:eu-repo/semantics/closedAccessAmp-activated protein kinase (ampk?)Endothelium-dependent relaxationEnosMethylglyoxalArticle25110911524127540Q3