Skip to main content
PMC 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
. 1993 Jul 1;90(13):5929–5933. doi: 10.1073/pnas.90.13.5929

Peroxidase-dependent metal-independent oxidation of low density lipoprotein in vitro: a model for in vivo oxidation?

E Wieland 1, S Parthasarathy 1, D Steinberg 1
PMCID: PMC46840  PMID: 8327462

Abstract

Oxidative modification of low density lipoprotein is believed to be an important pathway by which the lipoprotein becomes atherogenic. The in vitro systems for oxidative modification of low density lipoprotein thus far described all appear to depend upon the presence in the medium of free transition metal ions (copper or iron). In vivo, on the other hand, these metals are present almost exclusively in tightly complexed forms that do not catalyze oxidative modification. The present studies describe oxidation of low density lipoprotein in a simple system that does not depend upon the presence of added free metal ions. It requires the presence of horseradish peroxidase and either hydrogen peroxide or lipid hydroperoxides.

Full text

PDF
5929

Selected References

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

  1. Balla G., Jacob H. S., Eaton J. W., Belcher J. D., Vercellotti G. M. Hemin: a possible physiological mediator of low density lipoprotein oxidation and endothelial injury. Arterioscler Thromb. 1991 Nov-Dec;11(6):1700–1711. doi: 10.1161/01.atv.11.6.1700. [DOI] [PubMed] [Google Scholar]
  2. Björkhem I., Henriksson-Freyschuss A., Breuer O., Diczfalusy U., Berglund L., Henriksson P. The antioxidant butylated hydroxytoluene protects against atherosclerosis. Arterioscler Thromb. 1991 Jan-Feb;11(1):15–22. doi: 10.1161/01.atv.11.1.15. [DOI] [PubMed] [Google Scholar]
  3. Carew T. E., Schwenke D. C., Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7725–7729. doi: 10.1073/pnas.84.21.7725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chamulitrat W., Mason R. P. Lipid peroxyl radical intermediates in the peroxidation of polyunsaturated fatty acids by lipoxygenase. Direct electron spin resonance investigations. J Biol Chem. 1989 Dec 15;264(35):20968–20973. [PubMed] [Google Scholar]
  5. Esterbauer H., Gebicki J., Puhl H., Jürgens G. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic Biol Med. 1992 Oct;13(4):341–390. doi: 10.1016/0891-5849(92)90181-f. [DOI] [PubMed] [Google Scholar]
  6. Flitter W. D., Mason R. P. The horseradish peroxidase catalysed oxidation of deoxyribose sugars. Free Radic Res Commun. 1990;9(3-6):297–302. doi: 10.3109/10715769009145688. [DOI] [PubMed] [Google Scholar]
  7. Fong L. G., Parthasarathy S., Witztum J. L., Steinberg D. Nonenzymatic oxidative cleavage of peptide bonds in apoprotein B-100. J Lipid Res. 1987 Dec;28(12):1466–1477. [PubMed] [Google Scholar]
  8. Fruebis J., Parthasarathy S., Steinberg D. Evidence for a concerted reaction between lipid hydroperoxides and polypeptides. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10588–10592. doi: 10.1073/pnas.89.22.10588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Kim E. H., Sevanian A. Hematin- and peroxide-catalyzed peroxidation of phospholipid liposomes. Arch Biochem Biophys. 1991 Aug 1;288(2):324–330. doi: 10.1016/0003-9861(91)90202-t. [DOI] [PubMed] [Google Scholar]
  12. Kita T., Nagano Y., Yokode M., Ishii K., Kume N., Ooshima A., Yoshida H., Kawai C. Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5928–5931. doi: 10.1073/pnas.84.16.5928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Naruszewicz M., Carew T. E., Pittman R. C., Witztum J. L., Steinberg D. A novel mechanism by which probucol lowers low density lipoprotein levels demonstrated in the LDL receptor-deficient rabbit. J Lipid Res. 1984 Nov;25(11):1206–1213. [PubMed] [Google Scholar]
  16. Ohki S., Ogino N., Yamamoto S., Hayaishi O. Prostaglandin hydroperoxidase, an integral part of prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes. J Biol Chem. 1979 Feb 10;254(3):829–836. [PubMed] [Google Scholar]
  17. Paganga G., Rice-Evans C., Rule R., Leake D. The interaction between ruptured erythrocytes and low-density lipoproteins. FEBS Lett. 1992 Jun 1;303(2-3):154–158. doi: 10.1016/0014-5793(92)80508-e. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Parthasarathy S., Steinberg D., Witztum J. L. The role of oxidized low-density lipoproteins in the pathogenesis of atherosclerosis. Annu Rev Med. 1992;43:219–225. doi: 10.1146/annurev.me.43.020192.001251. [DOI] [PubMed] [Google Scholar]
  20. Samokyszyn V. M., Marnett L. J. Hydroperoxide-dependent cooxidation of 13-cis-retinoic acid by prostaglandin H synthase. J Biol Chem. 1987 Oct 15;262(29):14119–14133. [PubMed] [Google Scholar]
  21. Schreiber J., Mason R. P., Eling T. E. Carbon-centered free radical intermediates in the hematin- and ram seminal vesicle-catalyzed decomposition of fatty acid hydroperoxides. Arch Biochem Biophys. 1986 Nov 15;251(1):17–24. doi: 10.1016/0003-9861(86)90046-9. [DOI] [PubMed] [Google Scholar]
  22. Sparrow C. P., Doebber T. W., Olszewski J., Wu M. S., Ventre J., Stevens K. A., Chao Y. S. Low density lipoprotein is protected from oxidation and the progression of atherosclerosis is slowed in cholesterol-fed rabbits by the antioxidant N,N'-diphenyl-phenylenediamine. J Clin Invest. 1992 Jun;89(6):1885–1891. doi: 10.1172/JCI115793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sparrow C. P., Parthasarathy S., Steinberg D. Enzymatic modification of low density lipoprotein by purified lipoxygenase plus phospholipase A2 mimics cell-mediated oxidative modification. J Lipid Res. 1988 Jun;29(6):745–753. [PubMed] [Google Scholar]
  24. Steinberg D., Parthasarathy S., Carew T. E., Khoo J. C., Witztum J. L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915–924. doi: 10.1056/NEJM198904063201407. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Valoti M., Sipe H. J., Jr, Sgaragli G., Mason R. P. Free radical intermediates during peroxidase oxidation of 2-t-butyl-4-methoxyphenol, 2,6-di-t-butyl-4-methylphenol, and related phenol compounds. Arch Biochem Biophys. 1989 Mar;269(2):423–432. doi: 10.1016/0003-9861(89)90126-4. [DOI] [PubMed] [Google Scholar]
  28. Van der Zee J., Duling D. R., Mason R. P., Eling T. E. The oxidation of N-substituted aromatic amines by horseradish peroxidase. J Biol Chem. 1989 Nov 25;264(33):19828–19836. [PubMed] [Google Scholar]
  29. Verlangieri A. J., Bush M. J. Effects of d-alpha-tocopherol supplementation on experimentally induced primate atherosclerosis. J Am Coll Nutr. 1992 Apr;11(2):131–138. [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