Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1989 Sep 15;262(3):707–712. doi: 10.1042/bj2620707

The action of defined oxygen-centred free radicals on human low-density lipoprotein.

S Bedwell 1, R T Dean 1, W Jessup 1
PMCID: PMC1133332  PMID: 2556107

Abstract

The effects of defined oxygen-centred free radicals on human low-density lipoprotein (LDL) structure and receptor affinity are discussed in relation to the mechanisms of cell-mediated oxidative modification of LDL. Both hydroxyl (OH.) and hydroperoxyl (HO2.) radicals caused depletion of endogenous alpha-tocopherol and formation of hydroperoxides. Superoxide (O2-.) radicals produced only very limited oxidation, but could potentiate oxidation stimulated by the addition of Cu2+. All these radicals enhanced the net negative charge of intact LDL and induced fragmentation of apolipoprotein B-100 (apo B). OH. also caused cross-linking of apo B. Radical attack decreased the affinity of LDL for the fibroblast apo B/E receptor, but did not enhance its endocytosis by mouse macrophages.

Full text

PDF
707

Images in this article

710Fig. 3.
on p.710

Selected References

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

  1. 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]
  2. 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]
  3. Brown M. S., Goldstein J. L., Krieger M., Ho Y. K., Anderson R. G. Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins. J Cell Biol. 1979 Sep;82(3):597–613. doi: 10.1083/jcb.82.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burton G. W., Webb A., Ingold K. U. A mild, rapid, and efficient method of lipid extraction for use in determining vitamin E/lipid ratios. Lipids. 1985 Jan;20(1):29–39. doi: 10.1007/BF02534359. [DOI] [PubMed] [Google Scholar]
  5. Dean R. T., Thomas S. M., Garner A. Free-radical-mediated fragmentation of monoamine oxidase in the mitochondrial membrane. Roles for lipid radicals. Biochem J. 1986 Dec 1;240(2):489–494. doi: 10.1042/bj2400489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dean R. T., Thomas S. M., Vince G., Wolff S. P. Oxidation induced proteolysis and its possible restriction by some secondary protein modifications. Biomed Biochim Acta. 1986;45(11-12):1563–1573. [PubMed] [Google Scholar]
  7. Esterbauer H., Jürgens G., Quehenberger O., Koller E. Autoxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes. J Lipid Res. 1987 May;28(5):495–509. [PubMed] [Google Scholar]
  8. Fukuzawa K., Gebicki J. M. Oxidation of alpha-tocopherol in micelles and liposomes by the hydroxyl, perhydroxyl, and superoxide free radicals. Arch Biochem Biophys. 1983 Oct 1;226(1):242–251. doi: 10.1016/0003-9861(83)90290-4. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Heinecke J. W., Rosen H., Chait A. Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture. J Clin Invest. 1984 Nov;74(5):1890–1894. doi: 10.1172/JCI111609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Hicks M., Gebicki J. M. A spectrophotometric method for the determination of lipid hydroperoxides. Anal Biochem. 1979 Nov 1;99(2):249–253. doi: 10.1016/s0003-2697(79)80003-2. [DOI] [PubMed] [Google Scholar]
  14. Hunt J. V., Simpson J. A., Dean R. T. Hydroperoxide-mediated fragmentation of proteins. Biochem J. 1988 Feb 15;250(1):87–93. doi: 10.1042/bj2500087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jürgens G., Hoff H. F., Chisolm G. M., 3rd, Esterbauer H. Modification of human serum low density lipoprotein by oxidation--characterization and pathophysiological implications. Chem Phys Lipids. 1987 Nov-Dec;45(2-4):315–336. doi: 10.1016/0009-3084(87)90070-3. [DOI] [PubMed] [Google Scholar]
  16. Krieger M., Brown M. S., Goldstein J. L. Isolation of Chinese hamster cell mutants defective in the receptor-mediated endocytosis of low density lipoprotein. J Mol Biol. 1981 Aug 5;150(2):167–184. doi: 10.1016/0022-2836(81)90447-2. [DOI] [PubMed] [Google Scholar]
  17. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  18. Montgomery R. R., Nathan C. F., Cohn Z. A. Effects of reagent and cell-generated hydrogen peroxide on the properties of low density lipoprotein. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6631–6635. doi: 10.1073/pnas.83.17.6631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morel D. W., DiCorleto P. E., Chisolm G. M. Endothelial and smooth muscle cells alter low density lipoprotein in vitro by free radical oxidation. Arteriosclerosis. 1984 Jul-Aug;4(4):357–364. doi: 10.1161/01.atv.4.4.357. [DOI] [PubMed] [Google Scholar]
  20. Ohkuma S., Poole B. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3327–3331. doi: 10.1073/pnas.75.7.3327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Parthasarathy S., Fong L. G., Otero D., Steinberg D. Recognition of solubilized apoproteins from delipidated, oxidized low density lipoprotein (LDL) by the acetyl-LDL receptor. Proc Natl Acad Sci U S A. 1987 Jan;84(2):537–540. doi: 10.1073/pnas.84.2.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Parthasarathy S., Printz D. J., Boyd D., Joy L., Steinberg D. Macrophage oxidation of low density lipoprotein generates a modified form recognized by the scavenger receptor. Arteriosclerosis. 1986 Sep-Oct;6(5):505–510. doi: 10.1161/01.atv.6.5.505. [DOI] [PubMed] [Google Scholar]
  23. Quinn M. T., Parthasarathy S., Steinberg D. Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5949–5953. doi: 10.1073/pnas.82.17.5949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rankin S. M., Leake D. S. The modification of low density lipoproteins by macrophages by oxidation or proteolysis. Agents Actions Suppl. 1988;26:233–239. [PubMed] [Google Scholar]
  25. Schuh J., Fairclough G. F., Jr, Haschemeyer R. H. Oxygen-mediated heterogeneity of apo-low-density lipoprotein. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3173–3177. doi: 10.1073/pnas.75.7.3173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Steinbrecher U. P. Oxidation of human low density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxide decomposition products. J Biol Chem. 1987 Mar 15;262(8):3603–3608. [PubMed] [Google Scholar]
  27. 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]
  28. Steinbrecher U. P. Role of superoxide in endothelial-cell modification of low-density lipoproteins. Biochim Biophys Acta. 1988 Mar 4;959(1):20–30. doi: 10.1016/0005-2760(88)90145-2. [DOI] [PubMed] [Google Scholar]
  29. Thomas S. M., Jessup W., Gebicki J. M., Dean R. T. A continuous-flow automated assay for iodometric estimation of hydroperoxides. Anal Biochem. 1989 Feb 1;176(2):353–359. doi: 10.1016/0003-2697(89)90322-9. [DOI] [PubMed] [Google Scholar]
  30. Weisgraber K. H., Innerarity T. L., Mahley R. W. Role of lysine residues of plasma lipoproteins in high affinity binding to cell surface receptors on human fibroblasts. J Biol Chem. 1978 Dec 25;253(24):9053–9062. [PubMed] [Google Scholar]
  31. Wolff S. P., Dean R. T. Fragmentation of proteins by free radicals and its effect on their susceptibility to enzymic hydrolysis. Biochem J. 1986 Mar 1;234(2):399–403. doi: 10.1042/bj2340399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. van Hinsbergh V. W., Scheffer M., Havekes L., Kempen H. J. Role of endothelial cells and their products in the modification of low-density lipoproteins. Biochim Biophys Acta. 1986 Aug 14;878(1):49–64. doi: 10.1016/0005-2760(86)90343-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES