title: Lipoprotein lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent of scavenger receptor BI.
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 approximately 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.
authors.affiliation: Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Innere Medizin, Martinistrasse 52, 20246 Hamburg, Germany. Rinninger@uke.uni-hamburg.de
authors.forename: F
authors.initials: F
authors.lastname: Rinninger
authors.forename: M
authors.initials: M
authors.lastname: Brundert
authors.forename: I
authors.initials: I
authors.lastname: Brosch
authors.forename: N
authors.initials: N
authors.lastname: Donarski
authors.forename: R M
authors.initials: RM
authors.lastname: Budzinski
authors.forename: H
authors.initials: H
authors.lastname: Greten
mesh_terms: D000302:Adrenal Cortex; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D003001:Cloning, Molecular; D006224:Cricetinae; D004622:Embryo, Mammalian; D006801:Humans; D007553:Isotope Labeling; D007668:Kidney; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B; D014162:Transfection
chemical_list: D018955:CD36 Antigens; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D008071:Lipoprotein Lipase