title: ApoB-containing lipoproteins in apoE-deficient mice are not metabolized by the class B scavenger receptor BI.
abstract: The scavenger receptor class B type I (SR-BI) recognizes a broad variety of lipoprotein ligands, including HDL, LDL, and oxidized LDL. In this study, we investigated whether SR-BI plays a role in the metabolism of cholesterol-rich lipoprotein remnants that accumulate in apolipoprotein E (apoE)(-/-) mice. These particles have an unusual apolipoprotein composition compared with conventional VLDL and LDL, containing mostly apoB-48 as well as substantial amounts of apoA-I and apoA-IV. To study SR-BI activity in vivo, the receptor was overexpressed in apoE(-/-) mice by adenoviral vector-mediated gene transfer. An approximately 10-fold increase in liver SR-BI expression resulted in no detectable alterations in VLDL-sized particles and a modest depletion of cholesterol in intermediate density lipoprotein/LDL-sized lipoprotein particles. This decrease was not attributable to altered secretion of apoB-containing lipoproteins in SR-BI-overexpressing mice. To directly assess whether SR-BI metabolizes apoE(-/-) mouse lipoprotein remnants, in vitro assays were performed in both CHO cells and primary hepatocytes expressing high levels of SR-BI. This analysis showed a remarkable deficiency of these particles to serve as substrates for selective lipid uptake, despite high-affinity, high-capacity binding to SR-BI. Taken together, these data establish that SR-BI does not play a direct role in the metabolism of apoE(-/-) mouse lipoprotein remnants.
authors.affiliation: Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536, USA. nrwebb1@uky.edu
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Webb
authors.forename: Maria C
authors.initials: MC
authors.lastname: de Beer
authors.forename: Frederick C
authors.initials: FC
authors.lastname: de Beer
authors.forename: Deneys R
authors.initials: DR
authors.lastname: van der Westhuyzen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D008074:Lipoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B; D014161:Transduction, Genetic
chemical_list: D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008074:Lipoproteins; D008565:Membrane Proteins; D018110:Receptors, Lipoprotein; D011994:Recombinant Proteins; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B