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: Do Hyung Kim, Young Mi Seok, In Kyeom Kim, In-Kyu Lee, Seong Yun Jeong, Nam Ho Jeoung
• Journal: BMB reports (BMB Rep) Vol. 44 Issue 6 Pg. 415-20 (Jun 2011) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 21699756 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Vasoconstrictor Agents
• Phenylephrine
• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• rho-Associated Kinases
• rhoA GTP-Binding Protein
• Glucosamine

Topics

• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid (pharmacology)
• Animals
• Aorta (chemistry, drug effects, physiology)
• Glucosamine (pharmacology)
• Male
• Phenylephrine (pharmacology)
• Phosphorylation
• Protein Processing, Post-Translational
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Vasoconstriction (drug effects)
• Vasoconstrictor Agents (pharmacology)
• rho-Associated Kinases (metabolism)
• rhoA GTP-Binding Protein (metabolism)