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

BMB Reports

Nam Ho Jeoung^3,7¹  Do Hyung Kim^1,3²  Young Mi Seok^2⁵  In Kyeom Kim^2⁶  Seong Yun Jeong^6⁷  In-Kyu Lee^3,4,5⁸ 

[1] Department of Endocrinology and Metabolism, Kyungpook National University Hospital, Daegu 700-721, and Departments of^6;Departments of^1;Fundamental Medical and Pharmaceutical Sciences, Catholic University of Daegu CU Leaders’ College, Gyeongsan 712-702, Korea^8;Medical Life Science and^7;Medical Sciences^2;Pharmacology and Cardiovascular Research Institute^3;Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine^5;World Class University (WCU) program, and^4

关键词: Blood vessel constriction;    O-GlcNAcylation;   

DOI  :  

学科分类：生物化学/生物物理

来源: Korean Society for Biochemistry and Molecular Biology

【 摘 要 】

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.

【 授权许可】

Unknown