Alpha- and beta-xylosides modulate the synthesis of fibronectin and thrombospondin-1 by endothelial cells

A E Canfield, A B Sutton, D R Hiscock, J T Gallagher, A M Schor

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

We have previously shown that both p-nitrophenyl-alpha-D-xylopyranoside (alpha-xyloside) and p-nitrophenyl-beta-D-xylopyranoside (beta-xyloside) inhibit endothelial morphogenesis in vitro. In order to determine the mechanism for this inhibition, we have now investigated the effects of these compounds on the synthesis of proteoglycans and proteins by bovine aortic endothelial cells. Consistent with their well-recognised modes of action, beta-xyloside, but not alpha-xyloside, enhanced the secretion of free glycosaminoglycans into the medium. Furthermore, although both xylosides inhibited proteoglycan deposition into the cell layer/matrix, only beta-xyloside altered the nature of the proteoglycans synthesised by the cells. Both alpha- and beta-xylosides markedly inhibited total protein synthesis by endothelial cells in the absence of any effect on cell growth. This inhibition was time- and dose-dependent and was not due to the enzymatic release of p-nitrophenol by the cells. The synthesis of fibronectin and thrombospondin-1 were specifically and differentially modulated by both alpha- and beta-xylosides. That is, xylosides markedly reduced fibronectin levels relative to other proteins in both the medium and the cell layer/matrix. In contrast, the relative levels of thrombospondin-1 were increased in the xyloside-treated cultures both in terms of mRNA and protein. These studies demonstrate novel effects of xylosides on protein synthesis. Furthermore, they suggest that the inhibition of endothelial morphogenesis by xylosides may be due to the actions of these compounds on the synthesis of specific proteins.

Original languageEnglish
Pages (from-to)249-58
Number of pages10
JournalBiochimica et Biophysica Acta: General Subjects
Volume1200
Issue number3
DOIs
Publication statusPublished - 18 Aug 1994

Keywords

  • Animals
  • Cattle
  • Cells, Cultured
  • Endothelium, Vascular/cytology
  • Fibronectins/biosynthesis
  • Glycosaminoglycans/biosynthesis
  • Glycosides/pharmacology
  • Membrane Glycoproteins/biosynthesis
  • Proteoglycans/biosynthesis
  • Thrombospondins

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