title: Scavenger receptor B1 (SR-B1) substrates inhibit the selective uptake of high-density-lipoprotein cholesteryl esters by rat parenchymal liver cells.
abstract: High-density lipoprotein cholesteryl esters (HDL-CE) are selectively taken up by liver parenchymal cells without parallel apolipoprotein uptake, and this selective uptake route forms an important step in reverse cholesterol transport. Recent data from Acton, Rigotti, Landschulz, Xu, Hobbs and Krieger [(1996) Science 271, 518-520] provide evidence that scavenger receptor B (SR-B1) can mediate selective uptake of HDL-CE. In order to identify if selective uptake of HDL-CE by rat liver parenchymal cells can be mediated by a protein with scavenger receptor properties we performed competition experiments in vivo with substrates for scavenger receptors. Addition of either low-density lipoprotein (LDL), acetylated LDL (AcLDL) or oxidized LDL (OxLDL) only marginally (<10%) decreased the association of HDL particles to parenchymal cells as measured by 125I-labelled HDL. HDL-CE association was inhibited by AcLDL by 35%, while addition of OxLDL did inhibit HDL-CE association by 80%, thereby completely blocking the selective uptake of HDL-CE. Studies with HDL labelled with a fluorescent cholesteryl-ester analogue confirmed that OxLDL mediated complete inhibition of HDL-CE selective uptake by rat liver parenchymal cells. The inhibition of HDL-CE selective uptake by OxLDL was insensitive to the additional presence of polyinosinic acid (poly I), indicating that the inhibitory effect did not involve a poly I-sensitive site. Anionic phospholipid liposomes inhibited HDL-CE association by 40%, while neutral liposomes were ineffective. The inhibition of the selective uptake of HDL-CE in liver parenchymal cells by modified LDL, in particular OxLDL and anionic phospholipids suggests that, in liver, the SR-B1 is responsible for the efficient uptake of HDL-CE.
authors.affiliation: Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Fluiter
authors.forename: T J
authors.initials: TJ
authors.lastname: van Berkel
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D018955:CD36 Antigens / Q000502:physiology*; D002469:Cell Separation; D002788:Cholesterol Esters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013379:Substrate Specificity
chemical_list: D018955:CD36 Antigens; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D010743:Phospholipids; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; C099252:oxidized low density lipoprotein