Long-Term Methylglyoxal Treatment Causes Endothelial Dysfunction of Rat Isolated Mesenteric Artery
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概要
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Methylglyoxal (MGO) is a metabolite of glucose and likely related to pathogenesis of diabetes-related vascular complications including hypertension. In this study, long-term effects of MGO on endothelial function were examined. Rat isolated mesenteric artery was treated for 3 days with MGO using an organ culture method. The contractility, morphology, and protein expression of organ-cultured artery were examined. MGO (42 μM, 3 days) impaired acetylcholine (ACh: 1 nM–300 μM)-induced endothelium-dependent relaxation, while it had no effect on sodium nitroprusside (0.1 nM–10 μM)-induced endothelium-independent relaxation. MGO decreased ACh (3 μM)-induced nitric oxide (NO) production as measured by a fluorescence NO indicator, diaminofluorescein-2. Consistently, MGO inhibited ACh (3 μM)-induced phosphorylation of vasodilator stimulated phosphoprotein (an indicator of cyclic GMP production). MGO induced apoptosis in endothelium as detected by TdT-mediated dUTP-biotin nick-end labeling staining. MGO induced accumulation of superoxide in endothelium as detected by dihydroethidium staining. MGO decreased protein expression of endothelial NO synthase (eNOS). Gp91ds-tat (0.1 μM), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), prevented the impairment of endothelium-dependent relaxation and the decrease in eNOS protein caused by MGO. The present results demonstrated that long-term MGO treatment impairs endothelium-dependent relaxation through NOX-derived increased superoxide-mediated endothelial apoptosis.
著者
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Morita Tomoka
Laboratory Of Crop Science Program Of Agronomy Department Of Bioresource And Bioenvironment School O
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Okada Muneyoshi
Laboratory Of Veterinary Pharmacology School Of Veterinary Medicine Kitasato University
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Hara Yukio
Laboratory Of Veterinary Pharmacology School Of Veterinary Medicine Kitasato University
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Mukohda Masashi
Laboratory Of Veterinary Pharmacology School Of Veterinary Medicine Kitasato University
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YAMAWAKI Hideyuki
Laboratory of Veterinary Pharmacology, Kitasato University, Towada, Aomori 034–8628, Japan
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HARA Yukio
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, Japan
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YAMAWAKI Hideyuki
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, Japan
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MORITA Tomoka
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, Japan
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OKADA Muneyoshi
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, Japan
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MUKOHDA Masashi
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, Japan
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