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Journal of Lipid Research, Vol 37, 926-936, Copyright © 1996 by Lipid Research, Inc.
A Krapp, S Ahle, S Kersting, Y Hua, K Kneser, M Nielsen, J Gliemann and U Beisiegel
The uptake of triglyceride-rich lipoproteins has been described as being
mediated by apolipoprotein E and lipoprotein lipase (LpL). Proteoglycans,
the LDL-receptor, and the LDL receptor-related protein (LRP) are the
cellular acceptors. In addition to LpL, hepatic lipase (HL) has been shown
to bind to LRP. In this study, the role of HL in lipoprotein uptake was
investigated. Human chylomicrons and rabbit beta- VLDL were used as ligands
for human hepatoma cells, primary human hepalocytes, normal and
proteoglycan-deficient Chinese hamster ovary (CHO) cells, and normal and
LDL receptor-deficient human fibroblasts. We show that HL induces
stimulation of the uptake of chylomicrons and beta-VLDL into the different
cell lines. HL is known to bind to heparan sulfate, and experiments on
normal and proteoglycan-deficient CHO cells showed that cell surface
proteoglycans are essential for HL-mediated uptake of lipoproteins. To
exclude LDL receptor-mediated uptake. we performed experiments on LDL
receptor-deficient fibroblasts that demonstrated that the LDL receptor was
not important for the HL- mediated uptake of lipoproteins. Crosslinking
experiments confirmed the binding of HL to LRP on the cell surface. To
identify the region of HL involved in the interaction with LRP, we used a
C-terminal fragment of LpL, known to inhibit LpL-mediated uptake.
HL-mediated lipoprotein uptake was suppressed by this fragment. Our
experiments indicate that HL, like LpL, can mediate the uptake of
lipoproteins into cells, most probably via a C-terminal binding site. The
uptake, initiated by proteoglycan binding, is mediated by LRP.
ARTICLES
Hepatic lipase mediates the uptake of chylomicrons and beta-VLDL into cells via the LDL receptor-related protein (LRP)
Medical Clinic, University Hospital Hamburg, Germany.
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S. Y. Choi, I. J. Goldberg, L. K. Curtiss, and A. D. Cooper Interaction between ApoB and Hepatic Lipase Mediates the Uptake of ApoB-containing Lipoproteins J. Biol. Chem., August 7, 1998; 273(32): 20456 - 20462. [Abstract] [Full Text] [PDF]
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R. K. Avramoglu, J. Nimpf, R. S. McLeod, K. W. S. Ko, Y. Wang, D. FitzGerald, and Z. Yao Functional Expression of the Chicken Low Density Lipoprotein Receptor-related Protein in a Mutant Chinese Hamster Ovary Cell Line Restores Toxicity of Pseudomonas Exotoxin A and Degradation of alpha 2-Macroglobulin J. Biol. Chem., March 13, 1998; 273(11): 6057 - 6065. [Abstract] [Full Text] [PDF]
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I. J. Martins and T. G. Redgrave A 13CO2 breath test to assess the metabolism of triglyceride-rich lipoprotein remnants in mice J. Lipid Res., March 1, 1998; 39(3): 691 - 698. [Abstract] [Full Text]
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A. P. van Beek, H. H. J. J. van Barlingen, F. C. de Ruijter-Heijstek, H. Jansen, D. W. Erkelens, G. M. Dallinga-Thie, and T. W. A. de Bruin Preferential clearance of apoB-48-containing lipoproteins after heparin-induced lipolysis is modulated by lipoprotein lipase activity J. Lipid Res., February 1, 1998; 39(2): 322 - 332. [Abstract] [Full Text]
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H. L. Dichek, W. Brecht, J. Fan, Z.-S. Ji, S. P. A. McCormick, H. Akeefe, L. Conzo, D. A. Sanan, K. H. Weisgraber, S. G. Young, et al. Overexpression of Hepatic Lipase in Transgenic Mice Decreases Apolipoprotein B-containing and High Density Lipoproteins. EVIDENCE THAT HEPATIC LIPASE ACTS AS A LIGAND FOR LIPOPROTEIN UPTAKE J. Biol. Chem., January 23, 1998; 273(4): 1896 - 1903. [Abstract] [Full Text] [PDF]
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Z.-S. Ji, H. L. Dichek, R. D. Miranda, and R. W. Mahley Heparan Sulfate Proteoglycans Participate in Hepatic Lipaseand Apolipoprotein E-mediated Binding and Uptake of Plasma Lipoproteins, Including High Density Lipoproteins J. Biol. Chem., December 12, 1997; 272(50): 31285 - 31292. [Abstract] [Full Text] [PDF]
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H. Jansen, A. J. M. Verhoeven, L. Weeks, J. J. P. Kastelein, D. J. J. Halley, A. van den Ouweland, J. W. Jukema, J. C. Seidell, and J. C. Birkenhager Common C-to-T Substitution at Position -480 of the Hepatic Lipase Promoter Associated With a Lowered Lipase Activity in Coronary Artery Disease Patients Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 2837 - 2842. [Abstract] [Full Text]
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M. S. Nielsen, J. Brejning, R. Garcia, H. Zhang, M. R. Hayden, S. Vilaro, and J. Gliemann Segments in the C-terminal Folding Domain of Lipoprotein Lipase Important for Binding to the Low Density Lipoprotein Receptor-related Protein and to Heparan Sulfate Proteoglycans J. Biol. Chem., February 28, 1997; 272(9): 5821 - 5827. [Abstract] [Full Text] [PDF]
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