ALPHA-XYLOSIDE AND BETA-XYLOSIDE MODULATE THE SYNTHESIS OF FIBRONECTIN AND THROMBOSPONDIN-1 BY ENDOTHELIAL-CELLS

We have previously shown that both p-nitrophenyl-alpha-D-xylopyranosid e (alpha-xyloside) and p-nitrophenyl-beta-D-xylopyranoside (beta-xylos ide) inhibit endothelial morphogenesis in vitro. In order to determine the mechanism for this inhibition, we have now investigated the effec ts of these compounds on the synthesis of proteoglycans and proteins b y bovine aortic endothelial cells. Consistent with their well-recognis ed modes of action, beta-xyloside, but not alpha-xyloside, enhanced th e secretion of free glycosaminoglycans into the medium. Furthermore, a lthough both xylosides inhibited proteoglycan deposition into the cell layer/matrix, only beta-xyloside altered the nature of the proteoglyc ans 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-depen dent and was not due to the enzymatic release of p-nitrophenol by the cells. The synthesis of fibronectin and thrombospondin-1 were specific ally and differentially modulated by both alpha- and beta-xylosides. T hat is, xylosides markedly reduced fibronectin levels relative to othe r 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 dem onstrate novel effects of xylosides on protein synthesis. Furthermore, they suggest that the inhibition of endothelial morphogenesis by xylo sides may be due to the actions of these compounds on the synthesis of specific proteins.