Abstract
Scavenger receptor class B type I (SR-BI) mediates the selective uptake of HDL cholesteryl esters (CEs) by the liver. LPL promotes this selective lipid uptake independent of lipolysis. In this study, the role of SR-BI in the mechanism of this LPL-mediated increase in selective CE uptake was explored. Baby hamster kidney (BHK) cells were transfected with the SR-BI cDNA, and significant SR-BI expression could be detected in immunoblots, whereas no SR-BI was visualized in control cells. Y1-BS1 murine adrenocortical cells were cultured without or with adrenocorticotropic hormone, and cells with no detectable or with SR-BI were obtained. These cells incubated without or with LPL in medium containing 125I/[3H]cholesteryl oleyl ether-labeled HDL3; tetrahydrolipstatin inhibited the catalytic activity of LPL. In BHK and in Y1-BS1 cells without or with SR-BI expression, apparent HDL3 selective CE uptake ([3H]CEt–125I) was detectable. Cellular SR-BI expression promoted HDL3 selective CE uptake by ~250–1,900%. In BHK or Y1-BS1 cells, LPL mediated an increase in apparent selective CE uptake. Quantitatively, this stimulating LPL effect was very similar in control cells and in cells with SR-BI expression. The uptake of radiolabeled HDL3 was also investigated in human embryonal kidney 293 (HEK 293) cells that are an established SR-BI-deficient cell model. LPL stimulated [3H]cholesteryl oleyl ether uptake from labeled HDL3 by HEK 293 cells substantially, showing that LPL can induce selective CE uptake from HDL3 independent of SR-BI. To explore the role of cell surface proteoglycans on lipoprotein uptake, we induced proteoglycan deficiency by heparinase treatment. Proteoglycan deficiency decreased the LPL-mediated promotion of HDL3 selective CE uptake. In summary, evidence is presented that the stimulating effect of LPL on HDL3 selective CE uptake is independent of SR-BI and lipolysis. However, cell surface proteoglycans are required for the LPL action on selective CE uptake. It is suggested that pathways distinct from SR-BI mediate selective CE uptake from HDL.—Rinninger, F., M. Brundert, I. Brosch, N. Donarski, R. M. Budzinski, and H. Greten. Lipoprotein lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent of scavenger receptor BI.
Highlights
HDL-associated cholesteryl esters (CEs) are taken up by hepatocytes and steroidogenic cells selectively, that is, independently of HDL holo-particle internalization (1)
A band corresponding to this receptor could be detected in control Baby hamster kidney (BHK) cells and in BHK cells with Scavenger receptor class B type I (SR-BI) expression, and the respective signal was identical in both cell types
To elucidate the role of SR-BI in the mechanism of the LPL-mediated increase in HDL selective CE uptake, we have generated by transfection BHK cells, which stably express human SR-BI, and significant expression of this protein was detectable in immunoblots
Summary
HDL-associated cholesteryl esters (CEs) are taken up by hepatocytes and steroidogenic cells selectively, that is, independently of HDL holo-particle internalization (1). SR-BI deficiency in these rodents increases plasma HDL cholesterol and decreases HDL selective CE uptake by the liver (3, 4) These investigations provide evidence for a physiologic function of SR-BI in HDL metabolism in vivo. LPL is bound to the luminal side of capillaries and arteries and is abundant in muscle and adipose tissue (5) This enzyme hydrolyzes chylomicron- and VLDL-associated triglycerides to provide fatty acids to tissues as an energy source (5). LPL binds to cell surface proteoglycans and associates with lipoproteins as well (5, 10, 13) This “bridging” concentrates the lipoprotein particles on the cell surface and thereby facilitates their uptake. The latter may be mediated by cell surface heparan sulfate proteoglycans (10, 14) or by lipoprotein receptors (11, 12) Established ligands for this lipase-mediated particle uptake are chylomicrons, chylomicron remnants, -VLDL, and LDL (10–12, 14)
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