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. 1989 Jan 1;257(1):239–244. doi: 10.1042/bj2570239

Uptake of retinyl ester in HL-60 cells via the low-density-lipoprotein-receptor pathway.

K O Wathne 1, B Carlander 1, K R Norum 1, R Blomhoff 1
PMCID: PMC1135561  PMID: 2920014

Abstract

Newly absorbed retinol is transported in association with chylomicrons and their remnants. In addition, after intake of high doses of retinol, significant amounts are also found in low-density lipoprotein (LDL). As both chylomicron remnants and LDL may be taken up by cells via the LDL receptor, and retinoids inhibit proliferation of some leukaemic cells, we have studied the uptake of retinol in leukaemic cells via the LDL-receptor pathway. HL-60 cells contain saturable binding sites for LDL. The binding of LDL to its receptor has a dissociation constant of about 3.2 x 10(-9) M, and the number of receptors per cell was calculated to be about 2700. Uptake of 125I-LDL by HL-60 cells was increased 2-fold by preincubating the cells with mevinolin. The presence of specific receptors for LDL on HL-60 cells was further confirmed by the finding that exogenous LDL cholesterol was able to up-regulate the ACAT (acyl-CoA: cholesterol acyltransferase) activity of HL-60 cells. We then tested the uptake of retinyl ester in leukaemic cells via the LDL-receptor pathway. HL-60 cells were incubated with LDL or chylomicron remnants labelled with [3H]retinyl palmitate. Uptake of retinyl ester associated with both LDL and chylomicron remnants was observed. Furthermore, the presence of excess LDL decreased the uptake by 75-100%, supporting the hypothesis that the uptake of retinyl ester occurred via the LDL receptor in HL-60 cells.

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Selected References

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  1. Alberts A. W., Chen J., Kuron G., Hunt V., Huff J., Hoffman C., Rothrock J., Lopez M., Joshua H., Harris E. Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3957–3961. doi: 10.1073/pnas.77.7.3957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berr F., Kern F., Jr Plasma clearance of chylomicrons labeled with retinyl palmitate in healthy human subjects. J Lipid Res. 1984 Aug;25(8):805–812. [PubMed] [Google Scholar]
  3. Blomhoff R., Drevon C. A., Eskild W., Helgerud P., Norum K. R., Berg T. Clearance of acetyl low density lipoprotein by rat liver endothelial cells. Implications for hepatic cholesterol metabolism. J Biol Chem. 1984 Jul 25;259(14):8898–8903. [PubMed] [Google Scholar]
  4. Blomhoff R., Helgerud P., Rasmussen M., Berg T., Norum K. R. In vivo uptake of chylomicron [3H]retinyl ester by rat liver: evidence for retinol transfer from parenchymal to nonparenchymal cells. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7326–7330. doi: 10.1073/pnas.79.23.7326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blomhoff R., Rasmussen M., Nilsson A., Norum K. R., Berg T., Blaner W. S., Kato M., Mertz J. R., Goodman D. S., Eriksson U. Hepatic retinol metabolism. Distribution of retinoids, enzymes, and binding proteins in isolated rat liver cells. J Biol Chem. 1985 Nov 5;260(25):13560–13565. [PubMed] [Google Scholar]
  6. Breitman T. R., Selonick S. E., Collins S. J. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci U S A. 1980 May;77(5):2936–2940. doi: 10.1073/pnas.77.5.2936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brown M. S., Goldstein J. L. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34–47. doi: 10.1126/science.3513311. [DOI] [PubMed] [Google Scholar]
  8. Collins S. J., Ruscetti F. W., Gallagher R. E., Gallo R. C. Normal functional characteristics of cultured human promyelocytic leukemia cells (HL-60) after induction of differentiation by dimethylsulfoxide. J Exp Med. 1979 Apr 1;149(4):969–974. doi: 10.1084/jem.149.4.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drevon C. A. Cholesteryl ester metabolism in fat- and cholesterol/fat-fed guinea pigs. Atherosclerosis. 1978 Jun;30(2):123–136. doi: 10.1016/0021-9150(78)90055-2. [DOI] [PubMed] [Google Scholar]
  10. Drevon C. A., Weinstein D. B., Steinberg D. Regulation of cholesterol esterification and biosynthesis in monolayer cultures of normal adult rat hepatocytes. J Biol Chem. 1980 Oct 10;255(19):9128–9137. [PubMed] [Google Scholar]
  11. Florén C. H., Albers J. J., Kudchodkar B. J., Bierman E. L. Receptor-dependent uptake of human chylomicron remnants by cultured skin fibroblasts. J Biol Chem. 1981 Jan 10;256(1):425–433. [PubMed] [Google Scholar]
  12. Goldstein J. L., Basu S. K., Brown M. S. Receptor-mediated endocytosis of low-density lipoprotein in cultured cells. Methods Enzymol. 1983;98:241–260. doi: 10.1016/0076-6879(83)98152-1. [DOI] [PubMed] [Google Scholar]
  13. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ho Y. K., Smith R. G., Brown M. S., Goldstein J. L. Low-density lipoprotein (LDL) receptor activity in human acute myelogenous leukemia cells. Blood. 1978 Dec;52(6):1099–1114. [PubMed] [Google Scholar]
  15. Hui D. Y., Brecht W. J., Hall E. A., Friedman G., Innerarity T. L., Mahley R. W. Isolation and characterization of the apolipoprotein E receptor from canine and human liver. J Biol Chem. 1986 Mar 25;261(9):4256–4267. [PubMed] [Google Scholar]
  16. 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]
  17. Lie S. O., Wathne K. O., Petersen L. B., Slørdahl S. H., Norum K. R. High-dose retinol in children with acute myelogenous leukemia in remission. Eur J Haematol. 1988 May;40(5):460–465. doi: 10.1111/j.1600-0609.1988.tb00856.x. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Nilsson B. Probable in vivo induction of differentiation by retinoic acid of promyelocytes in acute promyelocytic leukaemia. Br J Haematol. 1984 Jul;57(3):365–371. doi: 10.1111/j.1365-2141.1984.tb02910.x. [DOI] [PubMed] [Google Scholar]
  20. Vitols S., Gahrton G., Ost A., Peterson C. Elevated low density lipoprotein receptor activity in leukemic cells with monocytic differentiation. Blood. 1984 May;63(5):1186–1193. [PubMed] [Google Scholar]
  21. Wathne K. O., Norum K. R., Smeland E., Blomhoff R. Retinol bound to physiological carrier molecules regulates growth and differentiation of myeloid leukemic cells. J Biol Chem. 1988 Jun 25;263(18):8691–8695. [PubMed] [Google Scholar]
  22. Wilson D. E., Chan I. F., Ball M. Plasma lipoprotein retinoids after vitamin A feeding in normal man: minimal appearance of retinyl esters among low-density lipoproteins. Metabolism. 1983 May;32(5):514–517. doi: 10.1016/0026-0495(83)90016-1. [DOI] [PubMed] [Google Scholar]

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