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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Glucosamine increases vascular contraction through activation of RhoA/Rho kinase pathway in isolated rat aorta

  • Kim, Do-Hyung (Department of Medical Sciences, Kyungpook National University School of Medicine) ;
  • Seok, Young-Mi (Department of Pharmacology and Cardiovascular Research Institute, Kyungpook National University School of Medicine) ;
  • Kim, In-Kyeom (Department of Pharmacology and Cardiovascular Research Institute, Kyungpook National University School of Medicine) ;
  • Lee, In-Kyu (Department of World Class University (WCU) program, Kyungpook National University School of Medicine) ;
  • Jeong, Seong-Yun (Department of Medical Life Science, Catholic University of Daegu CU Leaders' College) ;
  • Jeoung, Nam-Ho (Department of World Class University (WCU) program, Kyungpook National University School of Medicine)
  • Received : 2011.02.17
  • Accepted : 2011.05.06
  • Published : 2011.06.30
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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 MLC20$MLC_{20}$, 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.

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References

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