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Fat-Soluble Vitamins pp 345–390Cite as

The Molecular Action of α-Tocopherol in Lipoprotein Lipid Peroxidation

Pro- and Antioxidant Activity of Vitamin E in Complex Heterogeneous Lipid Emulsions

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Part of the book series: Subcellular Biochemistry ((SCBI,volume 30))

Abstract

Free radicals are inevitable by-products of biological redox reactions involving one-electron transfer processes such as those that occur during the catalytic cycles of some enzymes and electron transfer chains of mitochondria (Halliwell and Gutteridge, 1989). Radicals are also generated in biological systems as a result of exposure to a wide variety of external factors including some drugs, pollutants, metal ions, heat, UV or visible light, and other forms of radiation (Halliwell and Gutteridge, 1989). The generation of these reactive species in an uncontrolled fashion causes significant reversible or irreversible damage to a wide range of biological molecules including DNA, proteins, carbohydrates, and lipids. Many of these processes are chain reactions with a single initiating radical species damaging a large number of target molecules (Halliwell and Gutteridge, 1989). There is considerable interest in the reactions of these species, the damage they induce, and their relationship in the physiology and pathology of a variety of diseases and processes including cancer, arthritis, aging, and heart disease (Halliwell and Gutteridge, 1989). The “oxidative theory of atherosclerosis” proposes that oxidation of human low-density lipoprotein (LDL)* is implicated in the development of atherosclerosis (Steinberg et al., 1989; Y1ä-Herttuala et al., 1989; Steinbrecher et al., 1990; Witztum and Steinberg, 1991; Ross, 1993), the single largest cause of death in Western societies. The oxidation of different classes of biological macromolecules in isolation is well defined; however, less is known about oxidative processes in complex mixtures of lipids and proteins, such as lipoproteins, and the mechanisms inhibiting these deleterious processes.

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References

  • Anderson, M. M., Hazen, S. L., Hsu, F. F., and Heinecke, J. W., 1997, Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to convert hydroxyamino acids into glyceraldehyde, 2-hydroxypropanal, and acrolein. A mechanism for the generation of highly reactive α-hydroxy and α,β-unsaturaed aldehydes by phagocytes at sites of inflammation, J. Clin. Invest. 99:424–432.

    Article  PubMed  CAS  Google Scholar 

  • Aviram, M., Lund-Katz, S., Phillips, M. C., and Chait, A., 1988, The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprotein B-100 with cells, J. Biol. Chem. 263:16842–16848.

    PubMed  CAS  Google Scholar 

  • Barclay, L. R. C., Locke, S. J., and MacNeil, J. M., 1985, Autoxidation in micelles. Synergism of vitamin C with lipid-soluble vitamin E and water-soluble Trolox, Can. J. Chem. 63:366–374.

    Article  CAS  Google Scholar 

  • Barclay, L. R., Artz, J. D., and Mowat, J. J., 1995, Partitioning and antioxidant action of the water-soluble antioxidant, Trolox, between the aqueous and lipid phases of phosphatidylcholine membranes: 14C tracer and product studies, Biochim. Biophys. Acta 1237:77–85.

    Article  PubMed  Google Scholar 

  • Belkner, J., Wiesner, R., Rathman, J., Barnett, J., Sigal, E., and Kühn, H., 1993, Oxygenation of lipoproteins by mammalian lipoxygenases, Eur. J. Biochem. 213:251–261.

    Article  PubMed  CAS  Google Scholar 

  • Benz, D. J., Mol, M., Ezaki, M., Mori-Ito, N., Zelan, I., Miyanohara, A., Friedmann, T., Parthasarathy, S., Steinberg, D., and Witztum, J. L., 1995, Enhanced levels of lipoperoxides in low density lipoprotein incubated with murine fibroblast expressing high levels of human 15-lipoxygenase, J. Biol. Chem. 270:5191–5197.

    Article  PubMed  CAS  Google Scholar 

  • Boozer, C. E., Hammond, G. S., Hamilton, C. E., and Jyotirinda, N. S., 1955, Air oxidation of hydrocarbons. The stoichiometry and fate of inhibitors in benzene and chlorobenzene, J. Am. Chem. Soc. 77:3233–3237.

    Article  CAS  Google Scholar 

  • Bowry, V. W., and Stocker, R., 1993, Tocopherol-mediated peroxidation. The prooxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein, J. Am. Chem. Soc. 115:6029–6044.

    Article  CAS  Google Scholar 

  • Bowry, V. W., Ingold, K. U., and Stocker, R., 1992a, Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant, Biochem. J. 288:341–344.

    PubMed  CAS  Google Scholar 

  • Bowry, V. W., Stanley, K. K., and Stocker, R., 1992b, High density lipoprotein is the major carrier of lipid hydroperoxides in fasted human plasma, Proc. Natl. Acad. Sci. USA 89:10316–10320.

    Article  PubMed  CAS  Google Scholar 

  • Bowry, V. W., Mohr, D., Cleary, J., and Stocker, R., 1995, Prevention of tocopherol-mediated peroxidation of ubiquinol-10-free human low density lipoprotein, J. Biol. Chem. 270:5756–5763.

    Article  PubMed  CAS  Google Scholar 

  • Braun, S., and von Bruchhausen, F., 1994, Vitamin E or probucol as donors for oxidation of human low-density lipoprotein by peroxidases/H2O2, Pharmacology 49:325–335.

    Article  PubMed  CAS  Google Scholar 

  • Brooks, C. J. W., Harland, W. A., and Steel, G., 1966, Squalene, 26-hydroxycholesterol and 7-ketocholesterol in human atheromatous plaques, Biochim. Biophys. Acta 125:620–622.

    Article  PubMed  CAS  Google Scholar 

  • Brooks, C. J. W., Steel, G., Gilbert, J. D., and Harland, W. A., 1971, Lipids in human atheroma. Part 4. Characterisation of a new group of polar sterol esters from human atherosclerotic plaques, Atherosclerosis 13:223–237.

    Article  PubMed  CAS  Google Scholar 

  • Burton, G. W., and Ingold, K. U., 1981, Autoxidation of biological molecules. 1. The antioxidant activity of vitamin E and related chain-breaking phenolic antioxidants in vitro, J. Am. Chem. Soc. 103:6472–6477.

    Article  CAS  Google Scholar 

  • Burton, G. W., and Ingold, K. U., 1986, Vitamin E: Application of the principles of physical organic chemistry to the exploration of its structure and function, Acc. Chem. Res. 19:194–201.

    Article  CAS  Google Scholar 

  • Carpenter, K. L., Cheeseman, K. H., vander Veen, C., Taylor, S. E., Walker, M. K., and Mitchinson, M. J., 1995, Depletion of alpha-tocopherol in human atherosclerotic lesions, Free Radic. Res. 23:549–558.

    Article  PubMed  CAS  Google Scholar 

  • Chamulitrat, W., and Mason, R. P., 1989, Lipid peroxyl radical intermediates in the peroxidation of polyunsaturated fatty acids by lipoxygenase. Direct electron spin resonance investigations, J. Biol. Chem. 264:20968–20973.

    PubMed  CAS  Google Scholar 

  • Chance, B., Sies, H., and Boveris, A., 1979, Hydroperoxide metabolism in mammalian organs, Physiol. Rev. 59:527–605.

    PubMed  CAS  Google Scholar 

  • Chisolm, G. M., Ma, G., Irwin, K. C., Martin, L. L., Gunderson, K. G., Linberg, L. F., Morel, D. W., and DiCorleto, P. E., 1994, 7β-Hydroperoxycholest-5-en-3β-ol, a component of human atherosclerotic lesions, is the primary cytotoxin of oxidized human low density lipoprotein, Proc. Natl. Acad. Sci. USA 91:11452–11456.

    Article  PubMed  CAS  Google Scholar 

  • Christen, S., Peterhans, E., and Stocker, R., 1990, Antioxidant activities of some tryptophan metabolites: Possible implication for inflammatory diseases, Proc. Natl. Acad. Sci. USA 87:2506–2510.

    Article  PubMed  CAS  Google Scholar 

  • Christen, S., Southwell-Keely, P. T., and Stocker, R., 1992, Oxidation of 3-hydroxyanthranilic acid to the phenoxazinone cinnabarinic acid by peroxyl radicals and by compound I of peroxidases or catalase, Biochemistry 31:8090–8097.

    Article  PubMed  CAS  Google Scholar 

  • Christen, S., Thomas, S. R., Garner, B., and Stocker, R., 1994, Inhibition by interferon-γ of human mononuclear cell-mediated low density lipoprotein oxidation. Participation of tryptophan metabolism along the kynurenine pathway, J. Clin. Invest. 93:2149–2158.

    Article  PubMed  CAS  Google Scholar 

  • Constantinescu, A., Han, D., and Packer, L., 1993, Vitamin E recycling in human erythrocyte membranes, J. Biol. Chem. 268:10906–10913.

    PubMed  CAS  Google Scholar 

  • Cosgrove, J. P., Church, D. F., and Pryor, W. A., 1987, The kinetics of the autoxidation of polyunsaturated fatty acids, Lipids 22:299–304.

    Article  PubMed  CAS  Google Scholar 

  • Daugherty, A., Dunn, J. L., Rateri, D. L., and Heinecke, J. W., 1994, Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions, J. Clin. Invest. 94:437–444.

    Article  PubMed  CAS  Google Scholar 

  • Davies, M. J., and Slater, T. F., 1987, Studies on the metal-ion and lipoxygenase-catalysed breakdown of hydroperoxides using electron-spin-resonance spectroscopy, Biochem. J. 245:167–173.

    PubMed  CAS  Google Scholar 

  • Dieber-Rotheneder, M., Puhl, H., Waeg, G., Striegl, G., and Esterbauer, H., 1991, 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. 32:1325–1332.

    PubMed  CAS  Google Scholar 

  • Doba, T., Burton, G. W., and Ingold, K. U., 1985, Antioxidant and co-antioxidant activity of vitamin C. The effect of vitamin C., either alone or in the presence of vitamin E or a water-soluble vitamin E analogue, upon the peroxidation of aqueous multilamellar phospholipid liposomes, Biochim. Biophys. Acta 835:298–303.

    Article  PubMed  CAS  Google Scholar 

  • Eiserich, J. P., Cross, C. E., Jones, A. D., Halliwell, B., and van der Vliet, A., 1996, Formation of nitrating and chlorinating species by reaction of nitrite with hypochlorous acid. A novel mechanism for nitric oxide-mediated protein modification, J. Biol. Chem. 271:19199–19208.

    Article  PubMed  CAS  Google Scholar 

  • Esterbauer, H., Striegl, G., Puhl, H., and Rotheneder, M., 1989, Continuous monitoring of in vitro oxidation of human low density lipoprotein, Free Radic. Res. Commun. 6:67–75.

    Article  PubMed  CAS  Google Scholar 

  • Esterbauer, H., Dieber-Rotheneder, M., Striegl, G., and Waeg, G., 1991, Role of vitamin E in preventing the oxidation of low-density lipoprotein, Am. J. Clin. Nutr. 53:314S–321S.

    PubMed  CAS  Google Scholar 

  • Esterbauer, H., Gebicki, J., Puhl, H., and Jürgens, G., 1992, The role of lipid peroxidation and antioxidants in oxidative modification of LDL, Free Radic. Biol. Med. 13:341–390.

    Article  PubMed  CAS  Google Scholar 

  • Ezaki, M., Witztum, J. L., and Steinberg, D., 1995, Lipoperoxides in LDL incubated with fibroblasts that overexpress 15-lipoxygenase, J. Lipid. Res. 36:1996–2004.

    PubMed  CAS  Google Scholar 

  • Folcik, V. A., Nivar-Aristy, R. A., Krajewski, L. P., and Cathcart, M. K., 1995, Lipoxygenase contributes to the oxidation of lipids in human atherosclerotic plaques, J. Clin. Invest. 96:504–510.

    Article  PubMed  CAS  Google Scholar 

  • Frei, B., England, L., and Ames, B. N., 1989, Ascorbate is an outstanding antioxidant in human blood plasma, Proc. Natl. Acad. Sci. USA 86:6377–6381.

    Article  PubMed  CAS  Google Scholar 

  • Frei, B., Kim, M., et al., 1990, Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations, Proc. Natl. Acad. Sci. USA 87:4879–4883.

    Article  PubMed  CAS  Google Scholar 

  • Gilbert, J. D., Harland, W. A., Steel, G., and Brooks, C. J. W., 1969, The isolation and identification of 5α-cholestan-3β-ol from the human atheromatous aorta, Biochim. Biophys. Acta 187:453–456.

    Article  CAS  Google Scholar 

  • Gilbert, J. D., Brooks, C. J. W., and Harland, W. A., 1972, Lipids of human atheroma. VII. Isolation of diesters of cholest-5-ene-3βs, 26-diol from extracts of advanced atherosclerotic lesions of human aorta, Biochim. Biophys. Acta 270:149–155.

    Article  PubMed  CAS  Google Scholar 

  • Glavind, J., Hartmann, S., Clemmesen, J., Jessen, K. E., and Dam, H., 1952, Studies on the role of lipoperoxides in human pathology. II. The presence of peroxidized lipids in the atherosclerotic aorta, Acta Pathol. Microbiol. Scand. 30:1–6.

    Article  PubMed  CAS  Google Scholar 

  • Goldstein, J. L., and Brown, M. S., 1977, The low-density lipoprotein pathway and its relation to atherosclerosis, Annu. Rev. Biochem. 46:897–930.

    Article  PubMed  CAS  Google Scholar 

  • Graham, A., Hogg, N., Kalyanaraman, B., O’Leary, V., Darley-Usmar, V., and Moncada, S., 1993, Peroxynitrite modification of low-density lipoprotein leads to recognition by the macrophage scavenger receptor, FEBS Lett. 330:181–185.

    Article  PubMed  CAS  Google Scholar 

  • Gutteridge, J. M. C., Winyard, P. G., Blake, D. R., Lunec, J., Brailsford, S., and Halliwell, B., 1985, The behaviour of caeruloplasmin in stored human extracellular fluids in relation to ferroxidase II activity, lipid peroxidation and phenanthroline-detectable copper, Biochem. J. 230:517–523.

    PubMed  CAS  Google Scholar 

  • Halliwell, B., and Gutteridge, J. M. C., 1989, Free Radicals in Biology and Medicine, 2nd ed., Clarendon, Oxford.

    Google Scholar 

  • Halliwell, B., and Gutteridge, J. M. C., 1992, Biologically relevant metal ion-dependent hydroxyl radical generation. An update, FEBS Lett. 307:108–112.

    Article  PubMed  CAS  Google Scholar 

  • Hazell, L. J., and Stocker, R., 1993, Oxidation of low-density lipoprotein with hypochlorite causes transformation of the lipoprotein into a high-uptake form for macrophages, Biochem. J. 290:165–172.

    PubMed  CAS  Google Scholar 

  • Hazell, L. J., and Stocker, R., 1997, α-Tocopherol does not inhibit hypochlorite-induced oxidation of apolipoprotein B-100 of low-density lipoprotein, FEBS Lett. 414:541–544.

    Article  PubMed  CAS  Google Scholar 

  • Hazell, L. J., van den Berg, J. J. M., and Stocker, R., 1994, Oxidation of low-density lipoprotein by hypochlorite causes aggregation that is mediated by modification of lysine residues rather than lipid oxidation, Biochem. J. 302:297–304.

    PubMed  CAS  Google Scholar 

  • Hazell, L. J., Arnold, L., Flowers, D., Waeg, G., Malle, E., and Stocker, R., 1996, Presence of hypochlorite-modified proteins in human atherosclerotic lesions, J. Clin. Invest. 96:1535–1544.

    Article  Google Scholar 

  • Hazen, S. L., and Heinecke, J. W., 1997, 3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima, J. Clin. Invest. 99:2075–2081.

    Article  PubMed  CAS  Google Scholar 

  • Hazen, S. L., Gaut, S. P., Hsu, F. F., Crowley, J. R., d’Avignon, A., and Heinecke, J. W., 1997, p-Hydroxyphenylacetaldehyde, the major product of L-tyrosine oxidation by the myeloperoxidase-H2O2-chloride system of phagocytes, covalently modifies ε-amino groups of protein lysine residues, J. Biol. Chem. 272:16990–16998.

    Article  PubMed  CAS  Google Scholar 

  • Heinecke, J. W., Li, W., Francis, G. A., and Goldstein, J. A., 1993a, Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins, J. Clin. Invest. 91:2866–2872.

    Article  PubMed  CAS  Google Scholar 

  • Heinecke, J. W., Li, W., Daehnke, H. L., III, and Goldstein, J. A., 1993b, Dityrosine, a specific marker of oxidation, is synthesized by the myeloperoxidase-hydrogen peroxide system of human neutrophils and macrophages, J. Biol. Chem. 268:4069–4077.

    PubMed  CAS  Google Scholar 

  • Ingold, K. U., and Howard, J. A., 1962, Reaction of phenols with peroxy radicals, Nature 195:280–281.

    Article  CAS  Google Scholar 

  • Ingold, K. U., Bowry, V. W., Stocker, R., and Walling, C., 1993, Autoxidation of lipids and antioxidation by α-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids. The unrecognized consequences of lipid particle size as examplified by the oxidation of human low density lipoprotein, Proc. Natl. Acad. Sci. USA 90:45–49.

    Article  PubMed  CAS  Google Scholar 

  • Jessup, W., Mohr, D., Gieseg, S. P., Dean, R. T., and Stocker, R., 1992, The participation of nitric oxide in cell free-and its restriction of macrophage-mediated oxidation of low-density lipoprotein, Biochim. Biophys. Acta 1180:73–82.

    Article  PubMed  CAS  Google Scholar 

  • Jürgens, G., Hoff, H. F., Chisolm, G. M., and Esterbauer, H., 1987, Modification of human low density lipoprotein by oxidation—Characterization and pathophysiological implications, Chem. Phys. Lipids 45:315–336.

    Article  PubMed  Google Scholar 

  • Kagan, V. E., Serbinova, E. A., and Packer, L., 1990, Recycling and antioxidant activity of tocopherol homologs of differing hydrocarbon chain lengths in liver micrososmes, Arch. Biochem. Biophys. 282:221–225.

    Article  PubMed  CAS  Google Scholar 

  • Kagan, V. E., Serbinova, E. A., Forte, T., Scita, G., and Packer, L., 1992, Recycling of vitamin E in human low density lipoproteins, J. Lipid Res. 33:385–397.

    PubMed  CAS  Google Scholar 

  • Kalyanaraman, B., Antholine, W. E., and Parthasarathy, S., 1990, Oxidation of low-density lipoprotein by Cu2+ and lipoxygenase: An electron spin resonance study, Biochim. Biophys. Acta 1035, 3:286–292.

    Article  PubMed  CAS  Google Scholar 

  • Kalyanaraman, B., Darley-Usmar, V., Struck, A., Hogg, N., and Parthasarathy, S., 1995, Role of apolipoprotein B-derived radical and α-tocopheroxyl radical in peroxidase-dependent oxidation of low density lipoprotein, J. Lipid Res. 36:1037–1045.

    PubMed  CAS  Google Scholar 

  • Kenar, J. A., Havrilla, C. M., Porter, N. A., Guyton, J. R., Brown, S. A., Klemp, K. F., and Selinger, E., 1996, Identification and quantification of the regioisomeric cholesteryl linoleate hydroperoxides in oxidized human low density lipoprotein and high density lipoprotein, Chem. Res. Toxicol. 9:737–744.

    Article  PubMed  CAS  Google Scholar 

  • Kleinveld, H. A., Naber, A. H. J., Stalenhoef, A. F. H., and Demacker, P. N. M., 1993, Oxidation resistance, oxidation rate, and extent of oxidation of human low-density lipoprotein depend on the ratio of oleic acid content to linoleic acid content: Studies in vitamin E deficient subjects, Free Radic. Biol. Med. 15:273–280.

    Article  PubMed  CAS  Google Scholar 

  • Kleinveld, H. A., Demacker, P. N., and Stalenhoef, A. F., 1994, Comparative study on the effect of low-dose vitamin E and probucol on the susceptibility of LDL to oxidation and the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits, Arterioscler. Thromb. 14:1386–1391.

    Article  PubMed  CAS  Google Scholar 

  • Kohar, I., Baca, M., Suarna, C., Stocker, R., and Southwell-Keely, P., 1995, Is α-tocopherol a reservoir for α-tocopheryl hydroquinone? Free Radic. Biol. Med. 19:197–207.

    Article  PubMed  CAS  Google Scholar 

  • Kontush, A., Hübner, A., Finckh, C., Kohlschütter, B. A., and Beisiegel, U., 1994, Low density lipoprotein oxidizability by copper correlates to its initial ubiquinol-10 and polyunsaturated fatty acid content, FEBS Lett. 341:69–73.

    Article  PubMed  CAS  Google Scholar 

  • Kühn, H., Belkner, J., Wiesner, R., Schewe, T., Lankin, V. Z., and Tikhaze, A. K., 1992, Structure elucidation of oxygenated lipids in human atherosclerotic lesions, Eicosanoids 5:17–22.

    PubMed  Google Scholar 

  • Kühn, H., Barnett, J., Grunberger, D., Baecker, P., Chow, J., Nguyen, B., Bursztyn-Pettegrew, H., Chan, H., and Sigal, E., 1993, Overexpression, purification and characterization of human recombinant 15-lipoxygenase, Biochim. Biophys. Acta 1169:80–89.

    Article  PubMed  Google Scholar 

  • Kühn, H., Belkner, J., Suzuki, H., and Yamamoto, S., 1994a, Oxidative modification of human lipoproteins by lipoxygenases of different positional specificities, J. Lipid Res. 35:1749–1759.

    PubMed  Google Scholar 

  • Kuhn, H., Belkner, J., Zaiss, S., Fahrenklemper, T., and Wohlfeil, S., 1994b, Involvement of 15-lipoxygenase in early stages of atherogenesis, J. Exp. Med. 179:1903–1911.

    Article  PubMed  CAS  Google Scholar 

  • Kühn, H., Heydeck, D., Hogou, I., and Gniwotta, C., 1997, In vivo action of 15-lipoxygenase in early stage of human atherogenesis, J. Clin. Invest 99:888–893.

    Article  PubMed  Google Scholar 

  • Lass, A., Belkner, J., Esterbauer, H., and Kühn, H., 1996, Lipoxygenase treatment renders low-density lipoprotein susceptible to Cu2+-catalysed oxidation, Biochem. J. 314:577–585.

    PubMed  CAS  Google Scholar 

  • Leeuwenburgh, C., Rasmussen, J. E., Fong, F. H., Mueller, D. M., Pennathur, S., and Heinecke, J. W., 1997a, Mass spectrometric quantification of markers for protein oxidation by tyrosyl radical, copper and hydroxyl radical in low density lipoprotein isolated from human atherosclerotic plaques, J. Biol Chem. 272:3520–3526.

    Article  PubMed  CAS  Google Scholar 

  • Leeuwenburgh, C., Hardy, M. M., Hazen, S. L., Wagner, P., Oh-ishi, S., Steinbrecher, U. P., and Heinecke, J. W., 1997b, Reactive nitrogen intermediates promote low density lipoprotein oxidation in human atherosclerotic intima, J. Biol. Chem. 272:1433–1436.

    Article  PubMed  CAS  Google Scholar 

  • Loft, S., Strup, A., Buemann, B., and Poulsen, H. E., 1994, Oxidative DNA damage correlates with oxygen consumption in humans, FASEB J. 8:534–537.

    PubMed  CAS  Google Scholar 

  • Lynch, S. M., and Frei, B., 1995, Reduction of copper, but not iron, by human low density lipoprotein, LDL, Implications for metal ion-dependent oxidative modification of LDL, J. Biol. Chem. 270:5158–5163.

    Article  PubMed  CAS  Google Scholar 

  • Mohr, D., and Stocker, R., 1994, Radical-mediated oxidation of isolated human very low density lipoprotein, Arterioscler. Thromb. 14:1186–1192.

    Article  PubMed  CAS  Google Scholar 

  • Mohr, D., Bowry, V. W., and Stocker, R., 1992, Dietary supplementation with coenzyme Qlo results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low density lipoprotein to the initiation of lipid peroxidation, Biochim. Biophys. Acta 1126:247–254.

    Article  PubMed  CAS  Google Scholar 

  • Moreau, S., Davies, M. J., and Puppo, A., 1995, Reaction of ferric leghemoglobin with H2O2: Formation of heme-protein cross-links and dimeric species, Biochim. Biophys. Acta 1251:17–22.

    Article  PubMed  Google Scholar 

  • Mukai, K., Itoh, S., Itoh, S., and Morimoto, H., 1992, Stopped-flow kinetic study of vitamin E regeneration reaction with biological hydroquinones, reduced forms of ubiquinone, vitamin K, and tocopherolquinone in solution, J. Biol. Chem. 267:22277–22281.

    PubMed  CAS  Google Scholar 

  • Neuzil, J., and Stocker, R., 1994, Free and albumin-bound bilirubin is an efficient co-antioxidant for α-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation, J. Biol. Chem. 269:16712–16719.

    PubMed  CAS  Google Scholar 

  • Neuzil, J., Thomas, S. R., and Stocker, R., 1997a, Requirement for, promotion, or inhibition by α-tocopherol of radical-induced initiation of plasma lipoprotein lipid peroxidation, Free Radic. Biol Med. 22:57–71.

    Article  PubMed  CAS  Google Scholar 

  • Neuzil, J., Witting, P. K., and Stocker, R., 1997b, α-Tocopheryl hydroquinone is an efficient multifunctional inhibitor of radical-initiated oxidation of low-density lipoprotein lipids, Proc. Natl. Acad. Sci. USA 96:7885–7990.

    Article  Google Scholar 

  • O’Connell, A. M., Gieseg, S. P., and Stanley, K. K., 1994, Hypochlorite oxidation causes cross-linking of Lp(a), Biochim. Biochim. Acta 1225:180–186.

    Article  Google Scholar 

  • Ortiz de Montellano, P. R., and Catalano, C. E., 1985, Epoxidation of styrene by hemoglobin and myoglobin. Transfer of oxidizing equivalents to the protein surface, J. Biol. Chem. 260:9265–9271.

    PubMed  CAS  Google Scholar 

  • Ortiz de Montellano, P. R., and Grab, L. A., 1987, Cooxidation of styrene by horseradish peroxidase and phenols: A biochemical model for protein-mediated cooxidation, Biochemistry 26:5310–5314.

    Article  PubMed  CAS  Google Scholar 

  • Packer, J. E., Slater, T. F., and Willson, R. L., 1979, Direct observation of a free radical interaction between vitamin E and vitamin C., Nature 278:737–738.

    Article  PubMed  CAS  Google Scholar 

  • Panasenko, O. M., Evgina, S. A., Aidyraliev, R. K., Sergienko, V. I., and Vladimirov, Y. A., 1994, Peroxidation of human blood lipoproteins induced by exogenous hypochlorite or hypochlorite generated in the system of myeloperoxidase + H2O2 + Cl-, Free Radic. Biol. Med. 16:143–148.

    Article  PubMed  CAS  Google Scholar 

  • Parthasarathy, S., Wieland, E., and Steinberg, D., 1989, A role for endothelial cell lipoxygenase in the oxidative modification of low-density lipoprotein, Proc. Natl. Acad. Sci. USA 86:1046–1050.

    Article  PubMed  CAS  Google Scholar 

  • Parums, D. V., Brown, D. L., and Mitchinson, M. J., 1990, Serum antibodies to oxidized low-density lipoprotein and ceroid in chronic periaortitis, Arch. Pathol. Lab. Med. 114:383–386.

    PubMed  CAS  Google Scholar 

  • Peers, K. E., and Coxon, D. T., 1983, Controlled synthesis of monohydroperoxides by α-tocopherol inhibited autoxidation of polyunsaturated lipids, Chem. Phys. Lipids 32:49–56.

    Article  CAS  Google Scholar 

  • Porter, N. A., Weber, B. A., Weenen, H., and Khan, J. A., 1980, Autoxidation of polyunsaturated lipids. Factors controlling the stereochemistry of product hydroperoxides, J. Am. Chem. Soc. 102:5597–5601.

    Article  CAS  Google Scholar 

  • Porter, N. A., Lehman, L. S., Weber, B. A., and Smith, K. J., 1981, Unified mechanism for polyunsaturated fatty acid autoxidation. Competition of peroxy radical hydrogen atom abstraction, β-scission, and cyclization, J. Am. Chem. Soc. 103:6447–6455.

    Article  CAS  Google Scholar 

  • Reaven, P. D., Parthasarathy, S., Beltz, W. F., and Witztum, J. L., 1992, Effect of probucol dosage on plasma lipid and lipoprotein levels and on protection of low density lipoprotein against in vitro oxidation in humans, Arterioscler. Thromb. 12:318–324.

    Article  PubMed  CAS  Google Scholar 

  • Reaven, P. D., Khouw, A., Beltz, W. F., Parthasarathy, S., and Witztum, J. L., 1993, Effect of dietary antioxidant combinations in humans. Protection of LDL by vitamin E but not beta-carotene, Arterioscler. Thromb. 13:590–600.

    Article  PubMed  CAS  Google Scholar 

  • Ross, R., 1993, The pathogenesis of atheroslcerosis: A perspective for the 1990’s, Nature 362:801–809.

    Article  PubMed  CAS  Google Scholar 

  • Rubbo, H., Radi, R., Trujillo, M., Telleri, R., Kalyanaraman, B., Barnes, S., Kirk, M., and Freeman, B. A., 1994, Nitric oxide regulation of Superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives, J. Biol. Chem. 269:26066–26075.

    PubMed  CAS  Google Scholar 

  • Santanam, N., and Parthasarathy, S., 1995, Paradoxical actions of antioxidants in the oxidation of low density lipoprotein by peroxidases, J. Clin. Invest. 95:2594–2600.

    Article  PubMed  CAS  Google Scholar 

  • Sato, K., Niki, E., and Shimasaki, H., 1990, Free radical-mediated chain oxidation of low density lipoprotein and its synergistic inhibition by vitamin E and vitamin C, Arch. Biochem. Biophys. 279:402–405.

    Article  PubMed  CAS  Google Scholar 

  • Sattler, W., Kostner, G. M., Waeg, G., and Esterbauer, H., 1991, Oxidation of lipoprotein Lp(a), A comparison with low-density lipoproteins, Biochim. Biophys. Acta 1081:65–74.

    Article  PubMed  CAS  Google Scholar 

  • Sattler, W., Mohr, D., and Stocker, R., 1994, Rapid isolation of lipoproteins and assessment of their peroxidation by HPLC postcolumn chemiluminescence, Meth. Enzymol. 233:469–489.

    Article  PubMed  CAS  Google Scholar 

  • Savenkova, M. L., Mueller, D. M., and Heinecke, J. W., 1994, Tyrosyl radical generated by myeloperoxidase is a physiological catalyst for the initiation of lipid peroxidation in low density lipoprotein, J. Biol Chem. 269:20394–20400.

    PubMed  CAS  Google Scholar 

  • Sendobry, S. M., Cornicelli, J. A., Welch, K., Bocan, T., Tait, B., Trivedi, B. K., Colbry, N., Dyer, R. D., Feinmark, S. J., and Daugherty, A., 1997, Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties, Br. J. Pharmacol. 120:1199–1206.

    Article  PubMed  CAS  Google Scholar 

  • Schewe, T., Rapoport, S. M., and Kühn, H., 1986, Enzymology and physiology of reticulocyte lipoxygenase: Comparison with other lipoxygenases, in Advances in Enzymology and Related Areas of Molecular Biology, Vol. 58 (A. Meister, ed.), pp. 191–272, Wiley, New York.

    Google Scholar 

  • Sharma, M. K., and Buettner, G. R., 1993, Interaction of vitamin C and vitamin E during free radical stress in plasma: An ESR study, Free Rad. Biol. Med. 14:649–653.

    Article  PubMed  CAS  Google Scholar 

  • Shigenaga, M. K., Gimeno, C. J., and Ames, B. N., 1989, Urinary 8-hydroxy-2′-deoxyguanosine as a biological marker of in vivo oxidative DNA damage, Proc. Natl. Acad. Sci. USA 86:9697–9701.

    Article  PubMed  CAS  Google Scholar 

  • Sigal, E., Grunberger, D., Highland, E., Gross, C., Dixon, R. A. F., and Craik, C. S., 1990, Expression of cloned human reticulocyte 15-lipoxygenase and immunological evidence that 15-lipoxygenase of different cell types are related, J. Biol Chem. 265:5113–5120.

    PubMed  CAS  Google Scholar 

  • Smith, G., Mitchinson, M. J., Aruoma, O. I., and Halliwell, B., 1992, Stimulation of lipid peroxidation and hydroxyl-radical generation by the contents of human atherosclerotic lesions, Biochem. J. 286:901–905.

    PubMed  CAS  Google Scholar 

  • Steinberg, D., Parthasarathy, S., Carew, T. E., Khoo, J. C., and Witztum, J. L., 1989, Beyond cholesterol: Modifications of low-density lipoprotein that increase its atherogenicity, N. Engl. J. Med. 320:915–924.

    Article  PubMed  CAS  Google Scholar 

  • Steinbrecher, U. P., Zhang, H., and Lougheed, M., 1990, Role of oxidatively modified LDL in atherosclerosis, Free Radic. Biol. Med. 9:155–168.

    Article  PubMed  CAS  Google Scholar 

  • Stocker, R., 1990, Induction of haem oxygenase as a defence against oxidative stress, Free Radic. Res. Commun. 9:101–112.

    Article  PubMed  CAS  Google Scholar 

  • Stocker, R., 1994, Tracking the daily supplement, Today Life Sci. 6:24–31.

    Google Scholar 

  • Stocker, R., and Suarna, G., 1993, Extracellular reduction of ubiquinone-1 and-10 by human Hep G2 and blood cells, Biochim. Biophys. Acta 1158:15–22.

    Article  PubMed  CAS  Google Scholar 

  • Stocker, R., McDonagh, A. F., Glazer, A. N., and Ames, B. N., 1990, Antioxidant activities of bile pigments: Biliverdin and bilirubin, in Methods in Enzymology, Vol. 186 (L. Packer and A. N. Glazer, eds.), pp. 301–309, Academic Press, New York.

    Google Scholar 

  • Stocker, R., Bowry, V. W., and Frei, B., 1991, Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does α-tocopherol, Proc. Natl. Acad. Sci. USA 88:1646–1650.

    Article  PubMed  CAS  Google Scholar 

  • Suarna, C., Dean, R. T., May, J., and Stocker, R., 1995, Human atherosclerotic plaque contains both oxidized lipids and relatively large amounts of α-tocopherol and ascorbate, Arterioscler. Thromb. Vasc. Biol. 15:1616–1624.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki, H., Kurihara, Y., Takeya, M., Kamada, N., Kataoka, M., Jishage, K., Ueda, O., Sakaguchi, H., Higashi, T., Suzuki, T., Takashima, Y., Kawabe, Y., Cynshi, O., Wada, Y., Honda, M., Kurihara, H., Aburatani, H., Doi, T., Matsumoto, A., Azuma, S., Noda, T., Toyoda, Y., Itakura, H., Yazaki, Y., Horiuchi, S., Takahashi, K., Kruijt, J. K., van Berkel, T. J. C., Steinbrecher, U. P., Ishibashi, S., Maeda, N., Gordon, S., and Kodama, T., 1997, A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection, Nature 386:292–296.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, S. R., Neuzil, J., and Stocker, R., 1996a, Co-supplementation with coenzyme Q prevents the pro-oxidant effect of α-tocopherol and increases the resistance of lowdensity lipoprotein towards transition metal-dependent oxidation initiation, Arterioscler. Thromb. Vasc. Biol. 16:687–696.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, S. R., Witting, P. K., and Stocker, R., 1996b, 3-Hydroxyanthranilic acid is an efficient, cell-derived co-antioxidant for α-tocopherol, inhibiting human low density lipoprotein and plasma lipid peroxidation, J. Biol. Chem. 271:32714–32721.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, S. R., Davies, M. J., and Stocker, R., 1998, Oxidation and antioxidation of human low-density lipoprotein and plasma exposed to 3-morpholinosydnonimine and reagent peroxynitrite, Chem. Res. Toxicol. 11:484–494.

    Article  PubMed  CAS  Google Scholar 

  • Traber, M. G., Sokol, R. J., Burton, G. W., Ingold, K. U., Papas, A. M., Huffaker, J. E., and Kayden, H. J., 1990, Impaired ability of patients with familial isolated vitamin E deficiency to incorporate α-tocopherol, J. Clin. Invest. 85:397–407.

    Article  PubMed  CAS  Google Scholar 

  • Traber, M. G., Sokol, R. J., Kohlschütter, A., Yokota, T., Muller, D. P., Dufour, R., and Kayden, H. J., 1993, Impaired discrimination between stereoisomers of alpha-tocopherol in patients with familial isolated vitamin E deficiency, J. Lipid Res. 34:201–210.

    CAS  Google Scholar 

  • Upston, J. M., Neuzil, J., and Stocker, R., 1996, Oxidation of LDL by recombinant human 15-lipoxygenase: Evidence for α-tocopherol dependent oxidation of esterified core and surface lipids, J. Lipid Res. 37:2650–2661.

    PubMed  CAS  Google Scholar 

  • Upston, J. M., Neuzil, J., Witting, P. K., Alleva, R., and Stocker, R., 1997, Oxidation of free fatly acids in low density lipoprotein by 15-lipoxygenase stimulates nonenzymic, α-tocopherol-mediated peroxidation of cholesteryl esters, J. Biol. Chem. 272:30067–30074.

    Article  PubMed  CAS  Google Scholar 

  • van der Vliet, A., Eiserich, J. P., O’Neill, C. A., Halliwell, B., and Cross, C. E., 1995, Tyrosine modification by reactive nitrogen species: A closer look, Arch. Biochem. Biophys. 319:341–349.

    Article  PubMed  Google Scholar 

  • Wagner, J. R., Motchnik, P. A., Stocker, R., Sies, H., and Ames, B. N., 1993, The oxidation of blood plasma and low density lipoprotein components by chemically generated singlet oxygen, J. Biol. Chem. 268:18502–18506.

    PubMed  CAS  Google Scholar 

  • Waldeck, A. R., and Stocker, R., 1996, Radical-initiated lipid peroxidation in low density lipoproteins: Insights obtained from kinetic modeling, Chem. Res. Toxicol. 9:954–964.

    Article  PubMed  CAS  Google Scholar 

  • Wieland, E., Parthasarathy, S., and Steinberg, D., 1993, Peroxidase-dependent metal-independent oxidation of low density lipoprotein in vitro: A model for in vivo oxidation? Proc. Natl. Acad. Sci. USA 90:5929–5933.

    Article  PubMed  CAS  Google Scholar 

  • Wilcox, A. L., and Marnett, L. J., 1993, Polyunsaturated fatty acid alkoxyl radicals exist as carbon-centered epoxyallylic radicals: A key step in hydroperoxide-amplified lipid peroxidation, Chem. Res. Toxicol. 6:413–416.

    Article  PubMed  CAS  Google Scholar 

  • Wilks, A., and Ortiz de Montellano, P. R., 1992, Intramolecular translocation of the protein radical formed in the reaction of recombinant sperm whale myoglobin with H2O2, J. Biol. Chem. 267:8827–8833.

    PubMed  CAS  Google Scholar 

  • Witting, P. K., Bowry, V. W., and Stocker, R., 1995, Inverse deuterium kinetic isotope effect for peroxidation in human low-density lipoprotein, LDL: A simple test for tocopherol-mediated peroxidation of LDL lipids, FEBS Lett. 375:45–49.

    Article  PubMed  CAS  Google Scholar 

  • Witting, P. K., Westerlund, C., and Stocker, R., 1996, A rapid and simple screening test for potential inhibitors of tocopherol-mediated peroxidation of LDL lipids, J. Lipid Res. 37:853–867.

    PubMed  CAS  Google Scholar 

  • Witting, P. K., Upston, J. M., and Stocker, R., 1997, The role of α-tocopheroxyl radical in the initiation of lipid peroxidation in human low density lipoprotein exposed to horse radish peroxidase, Biochemistry 36:1251–1258.

    Article  PubMed  CAS  Google Scholar 

  • Witztum, J. L., and Steinberg, D., 1991, Role of oxidized low density lipoprotein in atherogenesis, J. Clin. Invest. 88:1785–1792.

    Article  PubMed  CAS  Google Scholar 

  • Y1ä-Herttuala, S., Palinski, S., Rosenfeld, M. E., Parthasarathy, S., Carew, T. E., Butler, S., Witztum, J. L., and Steinberg, D., 1989, Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man, J. Clin. Invest. 84:1086–1095.

    Article  Google Scholar 

  • Ylä-Herttuala, S., Rosenfeld, M. E., Parthasarathy, S., Glass, C. K., Sigal, E., Witztum, J. L., and Steinberg, D., 1990, 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. USA 87:6959–6963.

    Article  PubMed  Google Scholar 

  • Ylä-Herttuala, S., Luoma, J., Viita, H., Hiltunen, T., Sisto, T., and Nikkari, T., 1995, Transfer of 15-lipoxygenase gene into rabbit iliac arteries results in the appearance of oxidation-specific lipid-protein adducts characteristic of oxidized low density lipoprotein, J. Clin. Invest 95:2692–2698.

    Article  PubMed  Google Scholar 

  • Ziouzenkova, O., Gieseg, S. P., Ramos, P., and Esterbauer, H., 1996, Factors affecting resistance of low density lipoproteins to oxidation, Lipids 31:S71–S76.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Heart Research Institute, Camperdown, Sydney, NSW, 2050, Australia

    P. K. Witting, J. M. Upston & R. Stocker

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  1. P. K. Witting
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  2. J. M. Upston
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  1. King’s College London, University of London, London, UK

    Peter J. Quinn

  2. Department of Environmental and Occupational Health, and Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Valerian E. Kagan

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Witting, P.K., Upston, J.M., Stocker, R. (1998). The Molecular Action of α-Tocopherol in Lipoprotein Lipid Peroxidation. In: Quinn, P.J., Kagan, V.E. (eds) Fat-Soluble Vitamins. Subcellular Biochemistry, vol 30. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1789-8_15

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