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.
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September 1997
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Research Article|
September 01 1997
Scavenger receptor B1 (SR-B1) substrates inhibit the selective uptake of high-density-lipoprotein cholesteryl esters by rat parenchymal liver cells
Kees FLUITER;
Kees FLUITER
1Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, University of Leiden, Sylvius Laboratories, P.O. Box 9503, 2300 RA Leiden, The Netherlands
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Theo J. C. van BERKEL
Theo J. C. van BERKEL
1
1Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, University of Leiden, Sylvius Laboratories, P.O. Box 9503, 2300 RA Leiden, The Netherlands
1To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
January 21 1997
Revision Received:
April 04 1997
Accepted:
April 15 1997
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1997
1997
Biochem J (1997) 326 (2): 515–519.
Article history
Received:
January 21 1997
Revision Received:
April 04 1997
Accepted:
April 15 1997
Citation
Kees FLUITER, Theo J. C. van BERKEL; Scavenger receptor B1 (SR-B1) substrates inhibit the selective uptake of high-density-lipoprotein cholesteryl esters by rat parenchymal liver cells. Biochem J 1 September 1997; 326 (2): 515–519. doi: https://doi.org/10.1042/bj3260515
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