INTERACTION BETWEEN CADMIUM AND ZINC IN THE PRODUCTION AND SULFATION OF GLYCOSAMINOGLYCANS IN CULTURED BOVINE VASCULAR ENDOTHELIAL-CELLS

Previously, we showed that cadmium stimulates the production of glycos aminoglycans (GAGs) but inhibits their sulfation in cultured bovine ao rtic endothelial cells. The effect of zinc on such alterations of GAGs induced by cadmium was investigated in the present study. The incorpo ration of [H-3]glucosamine and [S-35]sulfate into GAGs was determined by the cetylpyridinium chloride precipitation method as a marker of GA G production and GAC sulfation, respectively. The incorporation of bot h [H-3]glucosamine and [S-35]sulfate was not changed in GAGs accumulat ed in the endothelial cell layer and the conditioned medium after expo sure to zinc at 20 mu M or less alone. A simultaneous exposure of the endothelial cell layer to zinc at 20 mu M or less and cadmium at 2 mu M resulted in prevention of the cadmium-induced decrease in [S-35]sulf ate incorporation; however, the cadmium-induced increase in [H-3]gluco samine incorporation was not affected by zinc. Characterization of GAG s in the cell layer revealed that such an interaction between zinc and cadmium occurred in both heparan sulfate and the other GAGs. Zinc sig nificantly prevented the inhibition of either [H-3]thymidine or [H-3]l eucine incorporation caused by cadmium with less accumulation of intra cellular cadmium, suggesting that zinc decreased intracellular cadmium and protected endothelial cells from cadmium-induced inhibition of DN A and protein synthesis. The present data showed that a simultaneous e xposure to cadmium and zinc resulted in an increase in heparan sulfate without a reduction of sulfation in the endothelial cell layer. The a lteration may potentiate the antithrombogenic property of vascular end othelium.