Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1991 Dec 1;280(Pt 2):359–365. doi: 10.1042/bj2800359

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.

M N Pieters 1, D Schouten 1, H F Bakkeren 1, B Esbach 1, A Brouwer 1, D L Knook 1, T J van Berkel 1
PMCID: PMC1130554  PMID: 1747108

Abstract

[3H]Cholesteryl ester-labelled human high-density lipoprotein (HDL) was injected into rats and its decay, intrahepatic cellular distribution and the kinetics of biliary secretion were determined. At 10 min after injection the hepatic uptake of cholesteryl esters from HDL was 3-fold higher as compared with the apolipoprotein. Selective uptake was exerted only by parenchymal cells (5.6-fold more cholesteryl esters than apolipoprotein) and not by liver endothelial or Kupffer cells. The kinetics of biliary secretion of processed cholesteryl esters initially associated with HDL or low-density lipoprotein (LDL) were compared in unrestrained rats, equipped with permanent catheters in bile duct, duodenum and heart. At 72 h after injection of [3H]cholesteryl oleate-labelled HDL, 51.0 +/- 2.5% of the injected dose was recovered as bile acids, which is about twice as high as the secretion of biliary radioactivity after injection of [3H]cholesteryl oleate-labelled LDL. Oestradiol treatment stimulated only liver uptake of LDL cholesteryl esters, and resulted in a 2-fold higher liver uptake than with HDL. However, the rate of radioactive bile acid formation from [3H]cholesteryl oleate-labelled HDL was still more rapid than for LDL. It is concluded that the selective uptake pathway for cholesteryl esters from HDL in parenchymal cells is more efficiently coupled to the formation of bile acids than is the cholesteryl ester uptake from LDL. This efficient coupling may facilitate the role of HDL in reverse cholesterol transport.

Full text

PDF
359

Selected References

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

  1. Arbeeny C. M., Rifici V. A., Eder H. A. The uptake of the apoprotein and cholesteryl ester of high-density lipoproteins by the perfused rat liver. Biochim Biophys Acta. 1987 Jan 13;917(1):9–17. doi: 10.1016/0005-2760(87)90277-3. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bachorik P. S., Franklin F. A., Virgil D. G., Kwiterovich P. O., Jr High-affinity uptake and degradation of apolipoprotein E free high-density lipoprotein and low-density lipoprotein in cultured porcine hepatocytes. Biochemistry. 1982 Oct 26;21(22):5675–5684. doi: 10.1021/bi00265a044. [DOI] [PubMed] [Google Scholar]
  4. Bakkeren H. F., Kuipers F., Vonk R. J., Van Berkel T. J. Evidence for reverse cholesterol transport in vivo from liver endothelial cells to parenchymal cells and bile by high-density lipoprotein. Biochem J. 1990 Jun 15;268(3):685–691. doi: 10.1042/bj2680685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barter P. J., Lally J. I. The activity of an esterified cholesterol transferring factor in human and rat serum. Biochim Biophys Acta. 1978 Nov 22;531(2):233–236. doi: 10.1016/0005-2760(78)90147-9. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Bonorris G. G., Coyne M. J., Chung A., Schoenfield L. J. Mechanism of estrogen-induced saturated bile in the hamster. J Lab Clin Med. 1977 Dec;90(6):963–970. [PubMed] [Google Scholar]
  8. Bravo E., Cantafora A. Hepatic uptake and processing of free cholesterol from different lipoproteins with and without sodium taurocholate administration. An in vivo study in the rat. Biochim Biophys Acta. 1990 Jun 28;1045(1):74–80. doi: 10.1016/0005-2760(90)90205-c. [DOI] [PubMed] [Google Scholar]
  9. Chao Y. S., Jones A. L., Hradek G. T., Windler E. E., Havel R. J. Autoradiographic localization of the sites of uptake, cellular transport, and catabolism of low density lipoproteins in the liver of normal and estrogen-treated rats. Proc Natl Acad Sci U S A. 1981 Jan;78(1):597–601. doi: 10.1073/pnas.78.1.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davis R. A., Elliott T. S., Lattier G. R., Showalter R. B., Kern F., Jr Regulation of bile acid synthesis via direct effects on the microsomal membrane. Biochemistry. 1986 Apr 8;25(7):1632–1636. doi: 10.1021/bi00355a028. [DOI] [PubMed] [Google Scholar]
  11. Davis R. A., Highsmith W. E., McNeal M. M., Schexnayder J. A., Kuan J. C. Bile acid synthesis by cultured hepatocytes. Inhibition by mevinolin, but not by bile acids. J Biol Chem. 1983 Apr 10;258(7):4079–4082. [PubMed] [Google Scholar]
  12. Davis R. A., Showalter R., Kern F., Jr Reversal by triton WR-1339 of ethynyloestradiol-induced hepatic cholesterol esterification. Biochem J. 1978 Jul 15;174(1):45–51. doi: 10.1042/bj1740045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ford R. P., Botham K. M., Suckling K. E., Boyd G. S. The effect of a rat plasma high-density lipoprotein subfraction on the synthesis of bile salts by rat hepatocyte monolayers. FEBS Lett. 1985 Jan 1;179(1):177–180. doi: 10.1016/0014-5793(85)80215-5. [DOI] [PubMed] [Google Scholar]
  14. Fry R. P., Mayes P. A., Suckling K. E., Botham K. M. The effect of chylomicron remnants on bile acid synthesis in cultured rat hepatocytes. Biochim Biophys Acta. 1990 Feb 23;1042(3):413–416. doi: 10.1016/0005-2760(90)90173-u. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Glomset J. A. The plasma lecithins:cholesterol acyltransferase reaction. J Lipid Res. 1968 Mar;9(2):155–167. [PubMed] [Google Scholar]
  18. Gwynne J. T., Mahaffee D. D. Rat adrenal uptake and metabolism of high density lipoprotein cholesteryl ester. J Biol Chem. 1989 May 15;264(14):8141–8150. [PubMed] [Google Scholar]
  19. Harkes L., Van Berkel J. C. Quantitative role of parenchymal and non-parenchymal liver cells in the uptake of [14C]sucrose-labelled low-density lipoprotein in vivo. Biochem J. 1984 Nov 15;224(1):21–27. doi: 10.1042/bj2240021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Harkes L., van Berkel T. J. Cellular localization of the receptor-dependent and receptor-independent uptake of human LDL in the liver of normal and 17 alpha-ethinyl estradiol-treated rats. FEBS Lett. 1983 Apr 5;154(1):75–80. doi: 10.1016/0014-5793(83)80878-3. [DOI] [PubMed] [Google Scholar]
  21. Herscovitz H., Ronen I., Bilu S., Tietz A. Bile acid synthesis from HDL cholesterol and cholesterol ester by cultured chick embryo hepatocytes. Biochim Biophys Acta. 1986 Oct 3;878(3):426–434. doi: 10.1016/0005-2760(86)90252-3. [DOI] [PubMed] [Google Scholar]
  22. Junker L. H., Davis R. A. Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes. J Lipid Res. 1989 Dec;30(12):1933–1941. [PubMed] [Google Scholar]
  23. Kleinherenbrink-Stins M. F., van der Boom J., Bakkeren H. F., Roholl P. J., Brouwer A., van Berkel T. J., Knook D. L. Light- and immunoelectron microscopic visualization of in vivo endocytosis of low density lipoprotein by hepatocytes and Kupffer cells in rat liver. Lab Invest. 1990 Jul;63(1):73–86. [PubMed] [Google Scholar]
  24. Kuipers F., Havinga R., Bosschieter H., Toorop G. P., Hindriks F. R., Vonk R. J. Enterohepatic circulation in the rat. Gastroenterology. 1985 Feb;88(2):403–411. doi: 10.1016/0016-5085(85)90499-8. [DOI] [PubMed] [Google Scholar]
  25. Kuipers F., Nagelkerke J. F., Bakkeren H., Havinga R., Van Berkel T. J., Vonk R. J. Processing of cholesteryl ester from low-density lipoproteins in the rat. Hepatic metabolism and biliary secretion after uptake by different hepatic cell types. Biochem J. 1989 Feb 1;257(3):699–704. doi: 10.1042/bj2570699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Leitersdorf E., Israeli A., Stein O., Eisenberg S., Stein Y. The role of apolipoproteins of HDL in the selective uptake of cholesteryl linoleyl ether by cultured rat and bovine adrenal cells. Biochim Biophys Acta. 1986 Oct 3;878(3):320–329. doi: 10.1016/0005-2760(86)90239-0. [DOI] [PubMed] [Google Scholar]
  28. Leitersdorf E., Stein O., Eisenberg S., Stein Y. Uptake of rat plasma HDL subfractions labeled with [3H]cholesteryl linoleyl ether or with 125I by cultured rat hepatocytes and adrenal cells. Biochim Biophys Acta. 1984 Oct 24;796(1):72–82. doi: 10.1016/0005-2760(84)90240-6. [DOI] [PubMed] [Google Scholar]
  29. Mackinnon A. M., Drevon C. A., Sand T. M., Davis R. A. Regulation of bile acid synthesis in cultured rat hepatocytes: stimulation by apoE-rich high density lipoproteins. J Lipid Res. 1987 Jul;28(7):847–855. [PubMed] [Google Scholar]
  30. 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]
  31. Miller N. E., La Ville A., Crook D. Direct evidence that reverse cholesterol transport is mediated by high-density lipoprotein in rabbit. Nature. 1985 Mar 7;314(6006):109–111. doi: 10.1038/314109a0. [DOI] [PubMed] [Google Scholar]
  32. Nagelkerke J. F., Bakkeren H. F., Kuipers F., Vonk R. J., van Berkel T. J. Hepatic processing of the cholesteryl ester from low density lipoprotein in the rat. J Biol Chem. 1986 Jul 5;261(19):8908–8913. [PubMed] [Google Scholar]
  33. Nagelkerke J. F., Barto K. P., van Berkel T. J. In vivo and in vitro uptake and degradation of acetylated low density lipoprotein by rat liver endothelial, Kupffer, and parenchymal cells. J Biol Chem. 1983 Oct 25;258(20):12221–12227. [PubMed] [Google Scholar]
  34. Ose L., Ose T., Norum K. R., Berg T. Uptake and degradation of 125I-labelled high density lipoproteins in rat liver cells in vivo and in vitro. Biochim Biophys Acta. 1979 Sep 28;574(3):521–536. doi: 10.1016/0005-2760(79)90248-0. [DOI] [PubMed] [Google Scholar]
  35. Ose L., Røken I., Norum K. R., Drevon C. A., Berg T. The binding of high density lipoproteins to isolated rat hepatocytes. Scand J Clin Lab Invest. 1981 Feb;41(1):63–73. doi: 10.3109/00365518109092016. [DOI] [PubMed] [Google Scholar]
  36. Pittman R. C., Attie A. D., Carew T. E., Steinberg D. Tissue sites of catabolism of rat and human low density lipoproteins in rats. Biochim Biophys Acta. 1982 Jan 15;710(1):7–14. doi: 10.1016/0005-2760(82)90183-7. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. 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]
  39. Rifici V. A., Eder H. A. A hepatocyte receptor for high-density lipoproteins specific for apolipoprotein A-I. J Biol Chem. 1984 Nov 25;259(22):13814–13818. [PubMed] [Google Scholar]
  40. Rinninger F., Pittman R. C. Regulation of the selective uptake of high density lipoprotein-associated cholesteryl esters by human fibroblasts and Hep G2 hepatoma cells. J Lipid Res. 1988 Sep;29(9):1179–1194. [PubMed] [Google Scholar]
  41. Rinninger F., Pittman R. C. Regulation of the selective uptake of high density lipoprotein-associated cholesteryl esters. J Lipid Res. 1987 Nov;28(11):1313–1325. [PubMed] [Google Scholar]
  42. Schouten D., Kleinherenbrink-Stins M. F., Brouwer A., Knook D. L., Kamps J. A., Kuiper J., van Berkel T. J. Characterization in vitro of interaction of human apolipoprotein E-free high density lipoprotein with human hepatocytes. Arteriosclerosis. 1990 Nov-Dec;10(6):1127–1135. doi: 10.1161/01.atv.10.6.1127. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Schwartz C. C., Halloran L. G., Vlahcevic Z. R., Gregory D. H., Swell L. Preferential utilization of free cholesterol from high-density lipoproteins for biliary cholesterol secretion in man. Science. 1978 Apr 7;200(4337):62–64. doi: 10.1126/science.204996. [DOI] [PubMed] [Google Scholar]
  45. Van Berkel T. J., Kruijt J. K., Van Gent T., Van Tol A. Saturable high affinity binding of low density and high density lipoprotein by parenchymal and non-parenchymal cells from rat liver. Biochem Biophys Res Commun. 1980 Feb 12;92(3):1002–1008. doi: 10.1016/0006-291x(80)90801-3. [DOI] [PubMed] [Google Scholar]
  46. Wandel M., Norum K. R., Berg T., Ose L. Binding, uptake, and degradation of 125I-labelled high-density lipoproteins in isolated non-parenchymal rat liver cells. Scand J Gastroenterol. 1981;16(1):71–80. [PubMed] [Google Scholar]
  47. 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]
  48. Whiting M. J., Wishart R. A., Lewis G., Mackinnon A. M. Bile acid synthesis by cultured rabbit hepatocytes: stimulation by three lipoprotein fractions. Biochim Biophys Acta. 1989 Sep 25;1005(2):137–142. doi: 10.1016/0005-2760(89)90179-3. [DOI] [PubMed] [Google Scholar]
  49. Wishart R., Mackinnon M. Uptake and metabolism of high-density lipoproteins by cultured rabbit hepatocytes. Biochim Biophys Acta. 1990 Jun 14;1044(3):375–381. doi: 10.1016/0005-2760(90)90083-a. [DOI] [PubMed] [Google Scholar]
  50. van Berkel T. J., Kruijt J. K., Kempen H. J. Specific targeting of high density lipoproteins to liver hepatocytes by incorporation of a tris-galactoside-terminated cholesterol derivative. J Biol Chem. 1985 Oct 5;260(22):12203–12207. [PubMed] [Google Scholar]

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

RESOURCES