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KMID : 0624620110440060415
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BMB Reports
2011 Volume.44 No. 6 p.415 ~ p.420
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Glucosamine increases vascular contraction through activation of RhoA/Rho kinase pathway in isolated rat aorta
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Kim Do-Hyung
Seok Young-Mi
Kim In-Kyeom
Lee In-Kyu
Jeong Seong-Yun
Jeoung Nam-Ho
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Abstract
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Diabetes is a well-known independent risk factor for vascular disease. However, its underlying mechanism remains unclear. It has been reported that increased influx of the hexosamine biosynthesis pathway (HBP) induces O-GlcNAcylation of proteins, leading to insulin resistance. In this study, we determined whether or not O-GlcNAc modification of proteins could increase vessel contraction. Using an endothelium-denuded aortic ring, we observed that glucosamine induced OGlcNAcylation of proteins and augmented vessel contraction stimulated by U46619, a thromboxane A(2) agonist, via augmentation of the phosphorylation of MLC(20), MYPT1(Thr855), and CPI17, but not phenylephrine. Pretreatment with OGT inhibitor significantly ameliorated glucosamine-induced vessel constriction. Glucosamine treatment also increased RhoA activity, which was also attenuated by OGT inhibitor. In conclusion, glucosamine, a product of glucose influx via the HBP in a diabetic state, increases vascular contraction, at least in part, through activation of the RhoA/Rho kinase pathway, which may be due to O-GlcNAcylation.
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KEYWORD
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Blood vessel constriction, O-GlcNAcylation, Diabetes, Hypertension, O-linked N-acetylglucosamine transferase, RhoA
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