title: Glyoxal causes inflammatory injury in human vascular endothelial cells.
abstract: To explore mechanisms of diabetes-associated vascular endothelial cells (ECs) injury, human umbilical vein ECs were treated for 24h with high glucose (HG; 26mM), advanced glycation end-products (AGEs; 100mug/ml) or their intermediate, glyoxal (GO: 50-5000muM). HG and AGEs had no effects on ECs morphology and inflammatory states as measured by vascular cell adhesion molecule (VCAM)-1 and cyclooxygenase (COX)-2 expressions. GO (500muM, 24h) induced cytotoxic morphological changes and protein expression of COX-2 but not VCAM-1. GO (500muM, 24h) activated ERK but not JNK, p38 or NF-kappaB. However, ERK inhibitor PD98059 was ineffective to GO-induced COX-2. While EUK134, synthetic combined superoxide dismutase/catalase mimetic, had no effect on GO-mediated inflammation, sodium nitroprusside inhibited it. The present results indicate that glyoxal, a metabolite of glucose might be a more powerful inducer for vascular ECs inflammatory injury. Nitric oxide but not anti-oxidant is preventive against GO-mediated inflammatory injury.
authors.affiliation: Department of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada, Aomori 034-8628, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamawaki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hara
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D044842:Cullin Proteins / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000201:enzymology / Q000209:etiology* / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism / Q000633:toxicity; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000633:toxicity; D006037:Glyoxal / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology; D015398:Signal Transduction; D014657:Vasculitis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology*
chemical_list: D000975:Antioxidants; C496871:CUL5 protein, human; D044842:Cullin Proteins; C433928:EUK-134; D005419:Flavonoids; D017127:Glycation End Products, Advanced; D020030:Nitric Oxide Donors; D009942:Organometallic Compounds; D047428:Protein Kinase Inhibitors; D012459:Salicylates; D006037:Glyoxal; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one