Increased expression of protein C-mannosylation in the aortic vessels of diabetic Zucker rats

Yoshito Ihara, Shino Manabe, Munetake Kanda, Hiroaki Kawano, Toshiyuki Nakayama, Ichiro Sekine, Takahito Kondo, Yukishige Ito

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

C-Mannosylation is a novel type of glycosylation in proteins. There are several examples of proteins in which the specific motif Trp-X-X-Trp is mannosylated at the first Trp to produce C-mannosylated Trp (CMW). Although C-mannosylation modifies Trp-X-X-Trp, predicted to be a functional motif of various integral proteins such as cytokine receptors, the physiological or pathological relevance of C-mannosylation in the cell is still not known. In this study, to characterize C-mannosylation in biological samples, we generated specific polyclonal antibodies against CMW by using a chemically synthesized CMW as an antigen. Using the antibody, we investigated the effect of hyperglycemic conditions on protein C-mannosylation in cultured cells and diabetic Zucker fatty rats. We found that protein C-mannosylation was increased in macrophage-like RAW264.7 cells under hyperglycemic conditions compared to low-glucose conditions. Furthermore, C-mannosylation was increased in the aortic vessel wall of Zucker fatty rats. Thrombospondin-1 was identified as a protein modified with C-mannosylation, and its expression was also increased in the aortic tissues of Zucker fatty rats. These results indicate that C-mannosylation is increased in specific tissues or cell types under hyperglycemic conditions, suggesting a pathological role for the increased C-mannosylation in the development of diabetic complications.

Original languageEnglish
Pages (from-to)383-392
Number of pages10
JournalGlycobiology
Volume15
Issue number4
DOIs
Publication statusPublished - 2005

Keywords

  • C-mannosylation
  • Diabetes
  • Hyperglycemia
  • Mannosyltransferase
  • Thrombospondin

ASJC Scopus subject areas

  • Biochemistry

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