Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein.
Chylomicron catabolism is known to be initiated by the enzyme lipoprotein lipase (triacylglycero-protein acylhydrolase, EC 3.1.1.34). Chylomicron remnants, produced by lipolysis, are rapidly taken up by the liver via an apolipoprotein E (apoE)-mediated, receptor-dependent process. The low density lipoprotein (LDL) receptor-related protein (LRP) has been suggested as the potential apoE receptor. We have analyzed the binding of human chylomicrons to HepG2 cells in the absence and presence of lipoprotein lipase. Bovine and human lipoprotein lipases were able to increase the specific binding of the chylomicrons by up to 30-fold. This effect was not dependent on lipolysis but appeared to be due to the lipase protein itself. It was not found when a structurally unrelated, bacterial lipase was used. Using beta-migrating very low density lipoproteins (beta-VLDLs), known as a good ligand for LRP, binding studies were performed on LDL receptor-negative human fibroblasts. The binding was increased 40-fold by addition of lipoprotein lipase. Crosslinking experiments on cells with 125I-labeled apoE liposomes or lipoprotein lipase showed that both proteins were able to bind to LRP on the cell surface. The binding of apoE to LRP was highly increased by the addition of lipase. We conclude that lipoprotein lipase strongly enhances the binding of apoE-containing lipoproteins to LRP and therefore might play an important role in chylomicron catabolism not only because of its lipolytic activity but also because of its structural properties.
Beisiegel
U
U
Medizinische Kernklinik und Poliklinik, Universitätskrankenhaus Eppendorf, Hamburg, Federal Republic of Germany.
Weber
W
W
Bengtsson-Olivecrona
G
G
D001057:Apolipoproteins E / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism*; D006801:Humans; D008071:Lipoprotein Lipase / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001057:Apolipoproteins E; D002914:Chylomicrons; D008079:Lipoproteins, VLDL; D008081:Liposomes; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D008071:Lipoprotein Lipase