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, Do-Hyung, Seok, Young-Mi, Kim, In-Kyeom, Lee, In-Kyu, Jeong, Seong-Yun, Jeoung, Nam-Ho
• Format: Journal Article
• Language: Korean
• Published: 생화학분자생물학회 30-06-2011
• Subjects: Blood vessel constriction; Diabetes; Hypertension; O-GlcNAcylation; O-Linked N-acetylglucosamine transferase; RhoA; Blood vessel constriction; Hypertension; O-GlcNAcylation; O-linked N-acetylglucosamine transferase; Diabetes; RhoA
• ISSN: 1976-6696; 1976-670X

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 MLC20, 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. [BMB reports 2011;44(6): 415-420]