Glucosamine increases vascular contraction through activation of RhoA/Rho kinase pathway in isolated rat aorta

• Published in: BMB reports Vol. 44; no. 6; pp. 415 - 420
• Main Authors: Kim, D.H., Kyungpook National University School of Medicine, Daegu, Republic of Korea, Seok, Y.M., Kyungpook National University School of Medicine, Daegu, Republic of Korea, Kim, I.K., Kyungpook National University School of Medicine, Daegu, Republic of Korea, Lee, I.K., Kyungpook National University School of Medicine, Daegu, Republic of Korea, Jeong, S.Y., Catholic University of Daegu CU Leaders' College, Gyeongsan, Republic of Korea, Jeoung, N.H., Kyungpook National University School of Medicine, Daegu, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Korea (South) 생화학분자생물학회 01.06.2011
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Animals; Aorta - chemistry; Aorta - drug effects; Aorta - physiology; Blood vessel constriction; DIABETE; DIABETES; Glucosamine - pharmacology; HIPERTENSION; HYPERTENSION; Male; O-GlcNAcylation; O-linked N-acetylglucosamine transferase; Phenylephrine - pharmacology; Phosphorylation; Protein Processing, Post-Translational; Rats; Rats, Sprague-Dawley; rho-Associated Kinases - metabolism; RhoA; rhoA GTP-Binding Protein - metabolism; Signal Transduction - drug effects; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2011.44.6.415

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 O-GlcNAcylation of proteins and augmented vessel contraction stimulated by U46619, a thromboxane A₂ 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.