HEPATIC LIPASE MEDIATES THE UPTAKE OF CHYLOMICRONS AND BETA-VLDL INTOCELLS VIA THE LDL RECEPTOR-RELATED PROTEIN (LRP)

The uptake of triglyceride-rich lipoproteins has been described as bei ng mediated by apoliprotein E and lipoprotein lipase (LpL). Proteoglyc ans, the LDL-receptor, and LDL receptor-related protein (LRP) are the cellular acceptors. In addition to LpL, hepatic lipase (HL) has been s hown to bind to LRP. In this study, the role of HL in lipoprotein upta ke was investigated. Human chylomicrons and rabbit beta-VLDL were used as ligands for human hepatoma cells, primary human hepatocytes, norma l and proteoglycan-deficient Chinese hamster ovary (CHO) cells, and no rmal and LDL receptor-deficient human fibroblasts. We show that HI ind uces stimulation of the uptake of chylomicrons and beta-heparan sulfat e, and experiments on normal and proteoglycan-deficient CHO cells show ed that cell surface proteoglycans are essential for HL-mediated uptak e of lipoproteins. to exclude LDL receptor-deficient fibroblasts that demonstrated that the LDL receptor was not important for the HL-mediat ed uptake of lipoproteins. Crosslinking experiments confirmed the bind ing of HL to LRP on the cell surface. To identify the region of HL inv olved in the interaction with LRP, we used a C-terminal fragment of LP L, known to inhibit LpL-mediated uptake. HL-mediated the uptake of lip oproteins into cells, most probably via a C-terminal binding site. The uptake, initiated by proteoglycan binding, is mediated by LRP.-Krapp, A., S. Able, S. Kersting, Y. Hua, K. Kneser, M. Nielsen, J. Gliemann, and U. Beisiegel. Hepatic lipase mediates the uptake of chylomicrons and beta-VLDL into cells via the LDL receptor-related protein (LRP).