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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antioxidants / pharmacology
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Cullin Proteins / metabolism
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Cyclooxygenase 2 / metabolism
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Diabetic Angiopathies / enzymology
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Diabetic Angiopathies / etiology*
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Diabetic Angiopathies / pathology*
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / enzymology
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Endothelium, Vascular / pathology*
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Flavonoids / pharmacology
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Glucose / metabolism
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Glucose / toxicity
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Glycation End Products, Advanced / metabolism
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Glycation End Products, Advanced / toxicity
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Glyoxal / antagonists & inhibitors
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Glyoxal / metabolism*
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Glyoxal / toxicity
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Humans
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Nitric Oxide Donors / pharmacology
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Organometallic Compounds / pharmacology
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Protein Kinase Inhibitors / pharmacology
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Salicylates / pharmacology
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Signal Transduction
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Vasculitis / enzymology
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Vasculitis / etiology*
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Vasculitis / pathology*
Substances
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Antioxidants
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CUL5 protein, human
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Cullin Proteins
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EUK-134
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Flavonoids
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Glycation End Products, Advanced
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Nitric Oxide Donors
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Organometallic Compounds
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Protein Kinase Inhibitors
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Salicylates
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Glyoxal
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Cyclooxygenase 2
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PTGS2 protein, human
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Extracellular Signal-Regulated MAP Kinases
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Glucose
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one