title: Glucosamine increases vascular contraction through activation of RhoA/Rho kinase pathway in isolated rat aorta.
abstract: 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.
authors.affiliation: Department of Medical Sciences, Catholic University of Daegu CU Leaders’ College, Gyeongsan 712-702, Korea.
authors.forename: Do Hyung
authors.initials: DH
authors.lastname: Kim
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Seok
authors.forename: In Kyeom
authors.initials: IK
authors.lastname: Kim
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Seong Yun
authors.initials: SY
authors.lastname: Jeong
authors.forename: Nam Ho
authors.initials: NH
authors.lastname: Jeoung
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology*; D005944:Glucosamine / Q000494:pharmacology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D005944:Glucosamine