The relevance of glycosaminoglycan sulfates to Apo E induced lipid uptake by hepatocyte monolayers.
The binding of Apolipoprotein E supplemented triglyceride emulsions to sulfated glycosaminoglycans demonstrated specificity for the carbohydrate polymers. Glucosamine containing glycosaminoglycans with relatively less sulfate had little affinity for the Apo E emulsion whereas those with more sulfate (i.e. heparin and sulfated heparans) effectively bound the emulsion. Galactosamine containing glycosaminoglycans (chondroitin 4 sulfate and dermatan sulfate) demonstrated no binding. The Apo E induced uptake of triglyceride emulsions by hepatocytes was inhibited by highly sulfated polysaccharides (i.e. heparin, dextran sulfate) but other glycosaminoglycans which did not bind the emulsion were ineffective in this inhibition. The same sulfated compounds which inhibited the hepatocyte Apo E emulsion interaction effectively released hepatic lipase from isolated heptic perfusions. Glycosaminoglycan sulfates which did not bind the Apo E supplemented emulsions and did not inhibit hepatocyte association were ineffective in releasing lipase. A heparan mixture isolated from human liver was much less effective in inhibiting Apo E induced association of emulsions with hepatocytes, than heparin. A highly sulfated octasaccharide fraction isolated from bovine liver heparin inhibited more effectively than the human heparans but less than the heparin. Inhibition of Apo E mediated hepatocyte emulsion association was produced by a one hour exposure of the cells to either heparinase or heparanase. The heparanase was more active than the heparinase and both were effective in the presence of protease inhibitors. Enzymes hydrolyzing chondroitin sulfates and hyaluronic acid were ineffective in inhibiting the Apo E induced association. The specific binding of human low density lipoprotein to the hepatocyte was much less effected by the heparanase exposure than the Apo E mediated binding.
D000818:Animals; D001056:Apolipoproteins C / Q000378:metabolism; D001057:Apolipoproteins E / Q000502:physiology*; D002478:Cells, Cultured; D004705:Endocytosis; D006025:Glycosaminoglycans / Q000502:physiology*; D006497:Heparan Sulfate / Q000502:physiology*; D066298:In Vitro Techniques; D008049:Lipase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009844:Oligosaccharides / Q000494:pharmacology; D051381:Rats; D013431:Sulfates; D014280:Triglycerides / Q000378:metabolism*
D001056:Apolipoproteins C; D001057:Apolipoproteins E; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D008049:Lipase; D009844:Oligosaccharides; D013431:Sulfates; D014280:Triglycerides