title: Scavenger receptor BI (SR-BI) mediates a higher selective cholesteryl ester uptake from LpA-I compared with LpA-I:A-II lipoprotein particles.
abstract: Scavenger receptor class B, type I (SR-BI) mediates the selective uptake of high-density lipoprotein- (HDL-) associated cholesteryl esters (CE), i.e. lipid uptake independent from HDL holo-particle internalisation. This pathway contributes to the HDL-mediated CE delivery to the liver. From human plasma HDL, two major lipoprotein subfractions can be isolated: one contains apolipoprotein (apo) A-I and apo A-II (LpA-I:A-II) as dominant protein components, whereas in the other population apo A-II is absent (LpA-I). In this investigation the role of SR-BI in selective CE uptake from HDL, LpA-I and LpA-I:A-II was explored. HDL(3) (d=1.125-1.21 g/ml), LpA-I and LpA-I:A-II were isolated from human plasma and radiolabeled in the protein (125I) as well as in the CE moiety ([3H]). Baby hamster kidney (BHK) cells were stably transfected with the full-length human SR-BI cDNA and these cells demonstrate SR-BI expression in immunoblots. In contrast, no SR-BI protein was detectable in control BHK cells (vector). To investigate lipoprotein uptake, cells incubated (37 degrees C, 4 h) in medium containing radiolabeled HDL(3), LpA-I or LpA-I:A-II and finally cellular tracer content was determined. For both types of BHK cells, the rate of apparent lipoprotein particle uptake according to the lipid tracer ([3H]) was in substantial excess over that due to the protein tracer (125I) demonstrating selective CE uptake ([3H]-(125)I) from HDL(3), LpA-I and LpA-I:A-II. SR-BI expression increased cellular selective CE uptake from labeled HDL(3) up to 24-fold. In BHK cells without SR-BI expression, selective CE uptake was higher from LpA-I compared with LpA-I:A-II. Analogously, in BHK cells with SR-BI expression, the rate of selective CE uptake was higher from LpA-I compared with LpA-I:A-II. In summary, SR-BI significantly increases selective CE uptake from HDL(3), LpA-I and LpA-I:A-II. Concerning HDL subfractions, the rate of SR-BI-mediated selective CE uptake is greater from LpA-I compared with LpA-I:A-II and this result suggests that SR-BI preferentially facilitates the CE transfer from LpA-I lipoprotein particles to cells.
authors.affiliation: Zentrum fuer Innere Medizin, Universitaetsklinikum Hamburg-Eppendorf, Universitaet Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. rinninger@uke.uni-hamburg.de
authors.forename: Franz
authors.initials: F
authors.lastname: Rinninger
authors.forename: May
authors.initials: M
authors.lastname: Brundert
authors.forename: Ralph-M
authors.initials: RM
authors.lastname: Budzinski
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Fruchart
authors.forename: Heiner
authors.initials: H
authors.lastname: Greten
authors.forename: Graciela R
authors.initials: GR
authors.lastname: Castro
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D016633:Apolipoprotein A-II / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism*; D006224:Cricetinae; D007668:Kidney / Q000378:metabolism*; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D018955:CD36 Antigens; D002788:Cholesterol Esters; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B