Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Jan;84(2):537–540. doi: 10.1073/pnas.84.2.537

Recognition of solubilized apoproteins from delipidated, oxidized low density lipoprotein (LDL) by the acetyl-LDL receptor.

S Parthasarathy, L G Fong, D Otero, D Steinberg
PMCID: PMC304244  PMID: 3467373

Abstract

Macrophages express a specific receptor that recognizes acetylated low density lipoprotein (LDL) and certain other chemically modified forms of LDL but not native LDL. LDL oxidatively modified either by incubation with endothelial cells in Ham's F-10 medium or by incubation with 5 microM copper(II) ion in the absence of cells is recognized by this same receptor. This oxidative modification, whether cell-induced or copper-catalyzed, is accompanied by many changes in the physical and chemical properties of LDL, including an increase in density, conversion of phosphatidylcholine to lysophosphatidylcholine, generation of lipid peroxides, and degradation of apolipoprotein B-100. Which changes are essential for eliciting the recognition by the receptor is not known. In the present paper it is shown that fragments of the degraded apolipoprotein from delipidated, oxidized LDL can be almost quantitatively resolubilized using n-octyl beta-D-glucopyranoside. These 125I-labeled, solubilized apoproteins were degraded rapidly by mouse peritoneal macrophages, and that degradation was competitively inhibited by unlabeled acetyl-LDL and endothelial cell-modified LDL but not by native LDL. These results show that the acetyl-LDL receptor recognizes an epitope on the apoprotein moiety, either newly generated or exposed as a result of oxidative modification, rather than some oxidized lipid moiety. Further, the results suggest that the lipids of oxidatively modified LDL do not play an obligatory role in determining the conformation of that epitope.

Full text

PDF
537

Selected References

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

  1. 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]
  2. Basu S. K., Goldstein J. L., Anderson G. W., Brown M. S. Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3178–3182. doi: 10.1073/pnas.73.9.3178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown M. S., Basu S. K., Falck J. R., Ho Y. K., Goldstein J. L. The scavenger cell pathway for lipoprotein degradation: specificity of the binding site that mediates the uptake of negatively-charged LDL by macrophages. J Supramol Struct. 1980;13(1):67–81. doi: 10.1002/jss.400130107. [DOI] [PubMed] [Google Scholar]
  4. Fogelman A. M., Shechter I., Seager J., Hokom M., Child J. S., Edwards P. A. Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2214–2218. doi: 10.1073/pnas.77.4.2214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fowler S., Shio H., Haley N. J. Characterization of lipid-laden aortic cells from cholesterol-fed rabbits. IV. Investigation of macrophage-like properties of aortic cell populations. Lab Invest. 1979 Oct;41(4):372–378. [PubMed] [Google Scholar]
  6. Gerrity R. G. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981 May;103(2):181–190. [PMC free article] [PubMed] [Google Scholar]
  7. Goldstein J. L., Ho Y. K., Basu S. K., Brown M. S. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci U S A. 1979 Jan;76(1):333–337. doi: 10.1073/pnas.76.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Haberland M. E., Fogelman A. M., Edwards P. A. Specificity of receptor-mediated recognition of malondialdehyde-modified low density lipoproteins. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1712–1716. doi: 10.1073/pnas.79.6.1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Haberland M. E., Fogelman A. M. Scavenger receptor-mediated recognition of maleyl bovine plasma albumin and the demaleylated protein in human monocyte macrophages. Proc Natl Acad Sci U S A. 1985 May;82(9):2693–2697. doi: 10.1073/pnas.82.9.2693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Haberland M. E., Olch C. L., Folgelman A. M. Role of lysines in mediating interaction of modified low density lipoproteins with the scavenger receptor of human monocyte macrophages. J Biol Chem. 1984 Sep 25;259(18):11305–11311. [PubMed] [Google Scholar]
  11. Haberland M. E., Rasmussen R. R., Olch C. L., Fogelman A. M. Two distinct receptors account for recognition of maleyl-albumin in human monocytes during differentiation in vitro. J Clin Invest. 1986 Mar;77(3):681–689. doi: 10.1172/JCI112362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Heinecke J. W., Baker L., Rosen H., Chait A. Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells. J Clin Invest. 1986 Mar;77(3):757–761. doi: 10.1172/JCI112371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Henriksen T., Mahoney E. M., Steinberg D. Enhanced macrophage degradation of biologically modified low density lipoprotein. Arteriosclerosis. 1983 Mar-Apr;3(2):149–159. doi: 10.1161/01.atv.3.2.149. [DOI] [PubMed] [Google Scholar]
  14. Henriksen T., Mahoney E. M., Steinberg D. Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6499–6503. doi: 10.1073/pnas.78.10.6499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Henriksen T., Mahoney E. M., Steinberg D. Interactions of plasma lipoproteins with endothelial cells. Ann N Y Acad Sci. 1982;401:102–116. doi: 10.1111/j.1749-6632.1982.tb25711.x. [DOI] [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. Parthasarathy S., Steinbrecher U. P., Barnett J., Witztum J. L., Steinberg D. Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc Natl Acad Sci U S A. 1985 May;82(9):3000–3004. doi: 10.1073/pnas.82.9.3000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schaffner T., Taylor K., Bartucci E. J., Fischer-Dzoga K., Beeson J. H., Glagov S., Wissler R. W. Arterial foam cells with distinctive immunomorphologic and histochemical features of macrophages. Am J Pathol. 1980 Jul;100(1):57–80. [PMC free article] [PubMed] [Google Scholar]
  19. Steinbrecher U. P., Parthasarathy S., Leake D. S., Witztum J. L., Steinberg D. Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3883–3887. doi: 10.1073/pnas.81.12.3883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Weinstein D. B., Carew T. E., Steinberg D. Uptake and degradation of low density lipoprotein by swine arterial smoot muscle cells with inhibition of cholesterol biosynthesis. Biochim Biophys Acta. 1976 Mar 26;424(3):404–421. doi: 10.1016/0005-2760(76)90030-8. [DOI] [PubMed] [Google Scholar]
  21. Yagi K. A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med. 1976 Apr;15(2):212–216. doi: 10.1016/0006-2944(76)90049-1. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES