Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1997 Sep 1;326(Pt 2):515–519. doi: 10.1042/bj3260515

Scavenger receptor B1 (SR-B1) substrates inhibit the selective uptake of high-density-lipoprotein cholesteryl esters by rat parenchymal liver cells.

K Fluiter 1, T J van Berkel 1
PMCID: PMC1218699  PMID: 9291126

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.

Full Text

The Full Text of this article is available as a PDF (310.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Acton S. L., Scherer P. E., Lodish H. F., Krieger M. Expression cloning of SR-BI, a CD36-related class B scavenger receptor. J Biol Chem. 1994 Aug 19;269(33):21003–21009. [PubMed] [Google Scholar]
  2. Acton S., Rigotti A., Landschulz K. T., Xu S., Hobbs H. H., Krieger M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science. 1996 Jan 26;271(5248):518–520. doi: 10.1126/science.271.5248.518. [DOI] [PubMed] [Google Scholar]
  3. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  4. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  5. Castro G. R., Fielding C. J. Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein. Biochemistry. 1988 Jan 12;27(1):25–29. doi: 10.1021/bi00401a005. [DOI] [PubMed] [Google Scholar]
  6. Fluiter K., Vietsch H., Biessen E. A., Kostner G. M., van Berkel T. J., Sattler W. Increased selective uptake in vivo and in vitro of oxidized cholesteryl esters from high-density lipoprotein by rat liver parenchymal cells. Biochem J. 1996 Oct 15;319(Pt 2):471–476. doi: 10.1042/bj3190471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Glass C., Pittman R. C., Civen M., Steinberg D. Uptake of high-density lipoprotein-associated apoprotein A-I and cholesterol esters by 16 tissues of the rat in vivo and by adrenal cells and hepatocytes in vitro. J Biol Chem. 1985 Jan 25;260(2):744–750. [PubMed] [Google Scholar]
  8. Glass C., Pittman R. C., Weinstein D. B., Steinberg D. Dissociation of tissue uptake of cholesterol ester from that of apoprotein A-I of rat plasma high density lipoprotein: selective delivery of cholesterol ester to liver, adrenal, and gonad. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5435–5439. doi: 10.1073/pnas.80.17.5435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Glomset J. A. The plasma lecithins:cholesterol acyltransferase reaction. J Lipid Res. 1968 Mar;9(2):155–167. [PubMed] [Google Scholar]
  10. Graf J., Boyer J. L. The use of isolated rat hepatocyte couplets in hepatobiliary physiology. J Hepatol. 1990 May;10(3):387–394. doi: 10.1016/0168-8278(90)90152-h. [DOI] [PubMed] [Google Scholar]
  11. Harkes L., van Berkel T. J. A saturable, high-affinity binding site for human low density lipoprotein on freshly isolated rat hepatocytes. Biochim Biophys Acta. 1982 Sep 14;712(3):677–683. doi: 10.1016/0005-2760(82)90297-1. [DOI] [PubMed] [Google Scholar]
  12. Hidaka H., Fidge N. H. Affinity purification of the hepatic high-density lipoprotein receptor identifies two acidic glycoproteins and enables further characterization of their binding properties. Biochem J. 1992 May 15;284(Pt 1):161–167. doi: 10.1042/bj2840161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johnson W. J., Mahlberg F. H., Rothblat G. H., Phillips M. C. Cholesterol transport between cells and high-density lipoproteins. Biochim Biophys Acta. 1991 Oct 1;1085(3):273–298. doi: 10.1016/0005-2760(91)90132-2. [DOI] [PubMed] [Google Scholar]
  14. Karlin J. B., Johnson W. J., Benedict C. R., Chacko G. K., Phillips M. C., Rothblat G. H. Cholesterol flux between cells and high density lipoprotein. Lack of relationship to specific binding of the lipoprotein to the cell surface. J Biol Chem. 1987 Sep 15;262(26):12557–12564. [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Landschulz K. T., Pathak R. K., Rigotti A., Krieger M., Hobbs H. H. Regulation of scavenger receptor, class B, type I, a high density lipoprotein receptor, in liver and steroidogenic tissues of the rat. J Clin Invest. 1996 Aug 15;98(4):984–995. doi: 10.1172/JCI118883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McFARLANE A. S. Efficient trace-labelling of proteins with iodine. Nature. 1958 Jul 5;182(4627):53–53. doi: 10.1038/182053a0. [DOI] [PubMed] [Google Scholar]
  18. McKnight G. L., Reasoner J., Gilbert T., Sundquist K. O., Hokland B., McKernan P. A., Champagne J., Johnson C. J., Bailey M. C., Holly R. Cloning and expression of a cellular high density lipoprotein-binding protein that is up-regulated by cholesterol loading of cells. J Biol Chem. 1992 Jun 15;267(17):12131–12141. [PubMed] [Google Scholar]
  19. Pearson A. M. Scavenger receptors in innate immunity. Curr Opin Immunol. 1996 Feb;8(1):20–28. doi: 10.1016/s0952-7915(96)80100-2. [DOI] [PubMed] [Google Scholar]
  20. Pieters M. N., Schouten D., Bakkeren H. F., Esbach B., Brouwer A., Knook D. L., van Berkel T. J. Selective uptake of cholesteryl esters from apolipoprotein-E-free high-density lipoproteins by rat parenchymal cells in vivo is efficiently coupled to bile acid synthesis. Biochem J. 1991 Dec 1;280(Pt 2):359–365. doi: 10.1042/bj2800359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pieters M. N., Schouten D., Van Berkel T. J. In vitro and in vivo evidence for the role of HDL in reverse cholesterol transport. Biochim Biophys Acta. 1994 Jan 11;1225(2):125–134. doi: 10.1016/0925-4439(94)90069-8. [DOI] [PubMed] [Google Scholar]
  22. Pittman R. C., Knecht T. P., Rosenbaum M. S., Taylor C. A., Jr A nonendocytotic mechanism for the selective uptake of high density lipoprotein-associated cholesterol esters. J Biol Chem. 1987 Feb 25;262(6):2443–2450. [PubMed] [Google Scholar]
  23. Redgrave T. G., Roberts D. C., West C. E. Separation of plasma lipoproteins by density-gradient ultracentrifugation. Anal Biochem. 1975 May 12;65(1-2):42–49. doi: 10.1016/0003-2697(75)90488-1. [DOI] [PubMed] [Google Scholar]
  24. Rigotti A., Acton S. L., Krieger M. The class B scavenger receptors SR-BI and CD36 are receptors for anionic phospholipids. J Biol Chem. 1995 Jul 7;270(27):16221–16224. doi: 10.1074/jbc.270.27.16221. [DOI] [PubMed] [Google Scholar]
  25. Rinninger F., Jaeckle S., Greten H., Windler E. Selective association of lipoprotein cholesteryl esters with liver plasma membranes. Biochim Biophys Acta. 1993 Feb 24;1166(2-3):284–299. doi: 10.1016/0005-2760(93)90109-m. [DOI] [PubMed] [Google Scholar]
  26. Schouten D., Kleinherenbrink-Stins M., Brouwer A., Knook D. L., Van Berkel T. J. Interaction in vivo and in vitro of apolipoprotein E-free high-density lipoprotein with parenchymal, endothelial and Kupffer cells from rat liver. Biochem J. 1988 Dec 1;256(2):615–621. doi: 10.1042/bj2560615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Van Berkel T. J., De Rijke Y. B., Kruijt J. K. Different fate in vivo of oxidatively modified low density lipoprotein and acetylated low density lipoprotein in rats. Recognition by various scavenger receptors on Kupffer and endothelial liver cells. J Biol Chem. 1991 Feb 5;266(4):2282–2289. [PubMed] [Google Scholar]
  28. Van Berkel T. J., Nagelkerke J. F., Harkes L., Kruijt J. K. Processing of acetylated human low-density lipoprotein by parenchymal and non-parenchymal liver cells. Involvement of calmodulin? Biochem J. 1982 Nov 15;208(2):493–503. doi: 10.1042/bj2080493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wang N., Weng W., Breslow J. L., Tall A. R. Scavenger receptor BI (SR-BI) is up-regulated in adrenal gland in apolipoprotein A-I and hepatic lipase knock-out mice as a response to depletion of cholesterol stores. In vivo evidence that SR-BI is a functional high density lipoprotein receptor under feedback control. J Biol Chem. 1996 Aug 30;271(35):21001–21004. doi: 10.1074/jbc.271.35.21001. [DOI] [PubMed] [Google Scholar]
  30. Weisgraber K. H., Mahley R. W. Subfractionation of human high density lipoproteins by heparin-Sepharose affinity chromatography. J Lipid Res. 1980 Mar;21(3):316–325. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES