Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1992 Mar 15;282(Pt 3):631–634. doi: 10.1042/bj2820631

Pro-oxidant effects of lipoxygenase-derived peroxides on the copper-initiated oxidation of low-density lipoprotein.

V J O'Leary 1, V M Darley-Usmar 1, L J Russell 1, D Stone 1
PMCID: PMC1130833  PMID: 1554346

Abstract

It has been proposed that lipoxygenases, specifically 15-lipoxygenase, may play an important role in promoting the oxidation of low-density lipoprotein (LDL) in the artery wall. It is well known that peroxides are unstable in the presence of transition metals, decomposing to form the alkoxy and peroxy radicals, and so initiating lipid peroxidation. To test whether lipoxygenase-derived peroxides may promote the oxidation of LDL in the presence of copper, the lipoprotein was enriched with lipid peroxides derived from the enzymic action of 5- and 15-lipoxygenases on either linoleic or arachidonic acid. All of these products were found to promote oxidation, whereas the related hydroxy fatty acids had no effect. This suggests that lipoxygenase-derived peroxides associated with the LDL particle may promote peroxidation in the presence of a suitable transition metal catalyst. This result has implications both for the mechanism of the potential pro-oxidant action of lipoxygenases in vivo and for the ex vivo assessment of the oxidizability of LDL samples isolated from different donors.

Full text

PDF
631

Selected References

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

  1. Bruckdorfer K. R., Jacobs M., Rice-Evans C. Endothelium-derived relaxing factor (nitric oxide), lipoprotein oxidation and atherosclerosis. Biochem Soc Trans. 1990 Dec;18(6):1061–1063. doi: 10.1042/bst0181061. [DOI] [PubMed] [Google Scholar]
  2. Cathcart M. K., McNally A. K., Chisolm G. M. Lipoxygenase-mediated transformation of human low density lipoprotein to an oxidized and cytotoxic complex. J Lipid Res. 1991 Jan;32(1):63–70. [PubMed] [Google Scholar]
  3. 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]
  4. Chung B. H., Wilkinson T., Geer J. C., Segrest J. P. Preparative and quantitative isolation of plasma lipoproteins: rapid, single discontinuous density gradient ultracentrifugation in a vertical rotor. J Lipid Res. 1980 Mar;21(3):284–291. [PubMed] [Google Scholar]
  5. Cominacini L., Garbin U., Davoli A., Micciolo R., Bosello O., Gaviraghi G., Scuro L. A., Pastorino A. M. A simple test for predisposition to LDL oxidation based on the fluorescence development during copper-catalyzed oxidative modification. J Lipid Res. 1991 Feb;32(2):349–358. [PubMed] [Google Scholar]
  6. Dieber-Rotheneder M., Puhl H., Waeg G., Striegl G., Esterbauer H. Effect of oral supplementation with D-alpha-tocopherol on the vitamin E content of human low density lipoproteins and resistance to oxidation. J Lipid Res. 1991 Aug;32(8):1325–1332. [PubMed] [Google Scholar]
  7. Esterbauer H., Dieber-Rotheneder M., Waeg G., Striegl G., Jürgens G. Biochemical, structural, and functional properties of oxidized low-density lipoprotein. Chem Res Toxicol. 1990 Mar-Apr;3(2):77–92. doi: 10.1021/tx00014a001. [DOI] [PubMed] [Google Scholar]
  8. Esterbauer H., Striegl G., Puhl H., Rotheneder M. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun. 1989;6(1):67–75. doi: 10.3109/10715768909073429. [DOI] [PubMed] [Google Scholar]
  9. Henriksson P., Hamberg M., Diczfalusy U. Formation of 15-HETE as a major hydroxyeicosatetraenoic acid in the atherosclerotic vessel wall. Biochim Biophys Acta. 1985 Apr 25;834(2):272–274. doi: 10.1016/0005-2760(85)90166-3. [DOI] [PubMed] [Google Scholar]
  10. Jessup W., Darley-Usmar V., O'Leary V., Bedwell S. 5-Lipoxygenase is not essential in macrophage-mediated oxidation of low-density lipoprotein. Biochem J. 1991 Aug 15;278(Pt 1):163–169. doi: 10.1042/bj2780163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jialal I., Freeman D. A., Grundy S. M. Varying susceptibility of different low density lipoproteins to oxidative modification. Arterioscler Thromb. 1991 May-Jun;11(3):482–488. doi: 10.1161/01.atv.11.3.482. [DOI] [PubMed] [Google Scholar]
  12. Kalyanaraman B., Antholine W. E., Parthasarathy S. Oxidation of low-density lipoprotein by Cu2+ and lipoxygenase: an electron spin resonance study. Biochim Biophys Acta. 1990 Sep 14;1035(3):286–292. doi: 10.1016/0304-4165(90)90090-j. [DOI] [PubMed] [Google Scholar]
  13. McNally A. K., Chisolm G. M., 3rd, Morel D. W., Cathcart M. K. Activated human monocytes oxidize low-density lipoprotein by a lipoxygenase-dependent pathway. J Immunol. 1990 Jul 1;145(1):254–259. [PubMed] [Google Scholar]
  14. Rankin S. M., Parthasarathy S., Steinberg D. Evidence for a dominant role of lipoxygenase(s) in the oxidation of LDL by mouse peritoneal macrophages. J Lipid Res. 1991 Mar;32(3):449–456. [PubMed] [Google Scholar]
  15. Regnström J., Walldius G., Carlson L. A., Nilsson J. Effect of probucol treatment on the susceptibility of low density lipoprotein isolated from hypercholesterolemic patients to become oxidatively modified in vitro. Atherosclerosis. 1990 May;82(1-2):43–51. doi: 10.1016/0021-9150(90)90142-6. [DOI] [PubMed] [Google Scholar]
  16. Salonen J. T., Salonen R., Seppänen K., Kantola M., Suntioinen S., Korpela H. Interactions of serum copper, selenium, and low density lipoprotein cholesterol in atherogenesis. BMJ. 1991 Mar 30;302(6779):756–760. doi: 10.1136/bmj.302.6779.756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schade U. F., Burmeister I., Engel R. Increased 13-hydroxyoctadecadienoic acid content in lipopolysaccharide stimulated macrophages. Biochem Biophys Res Commun. 1987 Sep 15;147(2):695–700. doi: 10.1016/0006-291x(87)90986-7. [DOI] [PubMed] [Google Scholar]
  18. Simon T. C., Makheja A. N., Bailey J. M. Formation of 15-hydroxyeicosatetraenoic acid (15-HETE) as the predominant eicosanoid in aortas from Watanabe Heritable Hyperlipidemic and cholesterol-fed rabbits. Atherosclerosis. 1989 Jan;75(1):31–38. doi: 10.1016/0021-9150(89)90204-9. [DOI] [PubMed] [Google Scholar]
  19. Simon T. C., Makheja A. N., Bailey J. M. Relationship of vascular 15-lipoxygenase induction to atherosclerotic plaque formation in rabbits. Prostaglandins Leukot Essent Fatty Acids. 1990 Dec;41(4):273–278. doi: 10.1016/0952-3278(90)90142-8. [DOI] [PubMed] [Google Scholar]
  20. Steinbrecher U. P., Witztum J. L., Parthasarathy S., Steinberg D. Decrease in reactive amino groups during oxidation or endothelial cell modification of LDL. Correlation with changes in receptor-mediated catabolism. Arteriosclerosis. 1987 Mar-Apr;7(2):135–143. doi: 10.1161/01.atv.7.2.135. [DOI] [PubMed] [Google Scholar]
  21. Steinbrecher U. P., Zhang H. F., Lougheed M. Role of oxidatively modified LDL in atherosclerosis. Free Radic Biol Med. 1990;9(2):155–168. doi: 10.1016/0891-5849(90)90119-4. [DOI] [PubMed] [Google Scholar]
  22. Stocker R., Bowry V. W., Frei B. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1646–1650. doi: 10.1073/pnas.88.5.1646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Thomas C. E., Jackson R. L. Lipid hydroperoxide involvement in copper-dependent and independent oxidation of low density lipoproteins. J Pharmacol Exp Ther. 1991 Mar;256(3):1182–1188. [PubMed] [Google Scholar]
  24. Ylä-Herttuala S., Palinski W., Rosenfeld M. E., Parthasarathy S., Carew T. E., Butler S., Witztum J. L., Steinberg D. Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest. 1989 Oct;84(4):1086–1095. doi: 10.1172/JCI114271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ylä-Herttuala S., Rosenfeld M. E., Parthasarathy S., Glass C. K., Sigal E., Witztum J. L., Steinberg D. Colocalization of 15-lipoxygenase mRNA and protein with epitopes of oxidized low density lipoprotein in macrophage-rich areas of atherosclerotic lesions. Proc Natl Acad Sci U S A. 1990 Sep;87(18):6959–6963. doi: 10.1073/pnas.87.18.6959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. el-Saadani M., Esterbauer H., el-Sayed M., Goher M., Nassar A. Y., Jürgens G. A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent. J Lipid Res. 1989 Apr;30(4):627–630. [PubMed] [Google Scholar]

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

RESOURCES