title: Methylglyoxal causes endothelial dysfunction: the role of endothelial nitric oxide synthase and AMP-activated protein kinase α.
abstract: BACKGROUND
  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 α (AMPKα) and its phosphorylated form at the threonine 172 site [p-AMPKα (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-AMPKα (Thr172) were significantly decreased without any change in total AMPKα 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-AMPKα (Thr172).
authors.forename: Saadet
authors.initials: S
authors.lastname: Turkseven
authors.forename: Elif
authors.initials: E
authors.lastname: Ertuna
authors.forename: Gunay
authors.initials: G
authors.lastname: Yetik-Anacak
authors.forename: Mukadder
authors.initials: M
authors.lastname: Yasa
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology*; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D066298:In Vitro Techniques; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000494:pharmacology*; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D018841:HSP90 Heat-Shock Proteins; D013481:Superoxides; D011765:Pyruvaldehyde; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases; D000109:Acetylcholine