Abstract
Myeloperoxidase is an enzyme in phagocytes which catalyzes several redox reactions. A major product is hypochlorous acid which appears to be important in inflammatory processes such as atherosclerosis. The aim of this study was to investigate whether the kinetics of low-density lipoprotein modification by the myeloperoxidase/hydrogen peroxide/chloride system in vitro conform to the established kinetics of hypochlorous acid formation and to compare the results with known in vivo data. The absorbance at 234 nm was applied to study the kinetics of the modification of low-density lipoprotein. Variation of the concentration of low-density lipoprotein, hydrogen peroxide, and chloride, respectively, had a biphasic effect on the maximal rate of low-density lipoprotein modification. Increasing the substrates up to certain threshold levels resulted in increased modification, however, further increases caused inhibition of low-density lipoprotein modification. The inhibitory effect of higher low-density lipoprotein concentrations might be relevant, since these concentrations occur in the human aortic intima. Furthermore, a positive correlation was found between the maximal rate of low-density lipoprotein modification and the acidity of the medium. In summary, low-density lipoprotein modification is affected by the myeloperoxidase/hydrogen peroxide/chloride system in a similar manner to hypochlorous acid production. We conclude that myeloperoxidase, which has been detected in atherosclerotic lesions, is able to modify low-density lipoprotein into the form which is taken up by macrophages in an uncontrolled manner.
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References
Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990 s. Nature 1993; 362:801.
Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986;232:34.
Schaffner T, Taylor K, Bartucci EJ, Fischer-Dzoga K, Beeson JH, Glagov S, Wissler RW. Arterial foam cells with distinctive immunomorphologic and histochemical features of macrophages. Am J Pathol 1980;100:57.
Daugherty A, Rateri DL, Dunn JL, Heinecke JW. Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions. J Clin Invest 1994;94:437.
Jerlich A, Fabjan JS, Tschabuschnig S, Smirnova AV, Horakova L, Hayn M, Auer H, Guttenberger H, Leis H-J, Tatzber F, Waeg G, Schaur RJ. Human low density lipoprotein as target of hypochlorite generated myeloperoxidase. Free Radic Biol Med 1998;24:1139.
Zgliczynski JK, Stelmaszynska T. The respiratory burst of neutrophilic granulocytes and its influence on infected tissues. In: Sbarra AJ, Strauss RR, eds. The respiratory burst and its physiological significance. New York: Plenum; 1988:315–347.
Aruoma OI, Halliwell B. Action of hypochlorous acid on the antioxidant protective enzymes superoxide dismutase, catalase and glutathione peroxidase. Biochem J 1987;248:973.
Sharonov BP, Govorova NI, Lyzlova SN. A comparative study of serum proteins ability to scavenge active oxygen species: O2− and OCl−. Biochem Int 1988;17:783.
Sharonov BP, Govorova NI, Lyzlova SN. Serum protein degradation by hypochlorite. Biochem Int 1989;19:27.
Panasenko OM, Evgina SA, Aidyraliev RK, Sergienko VI, Vladimirov YA. Peroxidation of human blood lipoproteins induced by exogenous hypochlorite generated in the system of myeloperoxidase+H2O2+Cl−. Free Radic Biol Med 1994;16:143.
Heinecke JW, Li W, Mueller DM, Boher A, Turk J. Cholesterol chlorohydrin synthesis by the myeloperoxidase-hydrogenperoxide-chloride system: potential markers for lipoproteins oxidatively damaged by phagocytes. Biochemistry 1994;33:10127.
Winterbourn CC, Van den Berg JJM, Roitman E, Kuypers FA. Chlorohydrine formation from unsaturated fatty acids reacted with hypochlorous acid. Arch Biochem Biophys 1992;296:547.
Hazell LJ, Arnold L, Flowers D, Waeg G, Malle E, Stocker R. Presence of hypochlorite-modified proteins in human atherosclerotic lesions. J Clin Invest 1996;97:1535.
Heinecke JW, Li W, Daenke HL, Goldsten JA. Dityrosine, a specific marker of oxidation, is synthesized by the myeloperoxidase-hydrogen peroxide system of human neutrophils and macrophages. J Biol Chem 1993;268:4069.
Heinecke JW, Li W, Francis GA, Goldsten JA. Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins. J Clin Invest 1993;91:2866.
Francis GA, Mendez AJ, Bierman EL, Heinecke JW. Oxidative tyrosylation of high density lipoprotein by peroxidase enhances cholesterol removal from cultered fibroblasts and macrophage foam cells. Proc Natl Acad Sci U S A 1993;90:6631.
Savenkova MI, Mueller DM, Heinecke JW. Tyrosyl radical generated myeloperoxidase is a physiological catalyst for the initiation of lipid peroxidation in low density lipoprotein. J Biol Chem 1994;269:20394.
Stelmaszynska T, Kukovetz E, Egger G, Schaur RJ. Possible involvement of myeloperoxidase in lipid peroxidation. Int J Biochem 1992;24:121.
Panasenko OM, Evgina SA, Driomina ES, Sharov VS, Sergienko VI, Vladimirov YA. Hypochlorite induces lipid peroxidation in blood lipoproteins and phospholipid liposomes. Free Radic Biol Med 1995;19:133.
Hazell JL, Van den Berg JJM, Stocker R. Oxidation of low density lipoprotein by hypochlorite causes aggregation that is mediated by modification of lysine residues rather than lipid oxidation. Biochem J 1994;302:297.
Kleinveld HA, Hak-Lemmers HLM, Stalenhoef AFH, Demacker PNM. Improved measurement of low-density-lipoprotein susceptibility to copper-induced oxidation: application of a short procedure for isolating low-density-lipoprotein. Clin Chem 1992;38:2066.
Bergmann AR, Ramos P, Esterbauer H, Winklhofer-Roob BM. RRR-∝ tocopherol can be substituted for by Trolox in determination of kinetic parameters of LDL oxidazability by copper. J Lipid Res 1997;38:2580.
Arnhold J, Wiegel D, Richter O, Hammerschmidt S, Arnold K, Krumbiegel M. Modification of low density lipoprotein by sodium hypochlorite. Biomed Biochim Acta 1991;50:967.
Leff JA, Repine JE. Neutrophil-mediated tissue injury. In: Abramson JS, Wheeler JG, eds. The neutrophil. Oxford: IRL Press; 1993:229–262.
Dean RT, Fu S, Stocker R, Davies ML. Biochemistry and pathology of radical-mediated protein oxidation. Biochem J 1997;324:1.
Chen Q, Esterbauer H, Jürgens G. Studies on epitopes on low-density lipoprotein modified by 4-hydroxynonenal. Biochemical characterization and determination. Biochem J 1992;288:249.
Suzuki M, Mori M, Miura S, Suematsu M, Fukumura D, Kimura H, Ishii H. Omeprazole attenuates oxygen-derived free radical production from human neutrophils. Free Radic Biol Med 1996;21:727.
Harper HA, Löffler G, Petrides PE, Weiss L. Physiologische Chemie. Berlin Heidelberg New York: Springer Verlag, 1995.
Roessner A, Vollmer E, Jaeger E, Rauterberg J, Böcker W. Differentiation and role of macrophages in the early human atherosclerotic plaque. In: Vollmer E, Roessner A, eds. Recent progress in atherosclerosis research. Berlin Heidelberg New York: Springer Verlag; 1993:59–71.
Prescott MF, McBride CK, Court M. Development of intimal lesions after leukocyte migration into the vascular wall. Am J Pathol 1989;135:835.
Kling D, Holzschuh T, Betz E. Recruitment and dynamics of leukocytes in the formation of arterial intimal thickening — a comparative study with normo-and hypercholesterolemic rabbits. Atherosclerosis 1993;101:79.
Völker W, Dorszewski A, Unruh V, Robenek H, Breithardt G, Buddecke E. Copper-induced inflammatory reactions of rat carotid arteries mimic restenosis/arteriosclerosis-like neointima formation. Atherosclerosis 1997;130:29.
Klebanoff SJ. Myeloperoxidase: occurrence and biological function. In: Everse J, Everse KE, Grisham MB, eds. Peroxidases in chemistry and biology, vol. 1. Boca Raton: CRC Press; 1991:1–36.
Andrews PC, Krinsky NI. A kinetic analysis of the interaction of human myeloperoxidase with hydrogen peroxide, chloride ions and protons. J Biol Chem 1982;257:13240.
Winterbourn CC, Garcia R, Segal AW. Production of the superoxide adduct of myeloperoxidase (compound III) by stimulated neutrophils, and its reactivity with H2O2 and chloride. Biochem J 1985;228:583.
Matheson NR, Travis J. Differential effects of oxidizing agents on human plasma alpha1-proteinase inhibitor and human neutrophil myeloperoxidase. Biochemistry 1985;24:1941.
Zgliczynski JM, Stelmaszynska T, Ostrowiski W, Naskalski J, Sznajd J. Myeloperoxidase of human leukemic leucocytes. Oxidation of amino acids in the presence of hydrogen peroxide. Eur J Biochem 1968;4:540.
Zgliczynski JM. Characteristics of myeloperoxidase from neutrophils and other peroxidases from different cell types. In: Sbarra AJ, Strauss RR, eds. The reticuloendothelial system. A comprehensive treatise, 2. Biochemistry and metabolism. New York: Plenum; 1980:255–278.
Weening RS, Roos D, Loos JA. Oxygen consumption of phagocytizing cells in human leukocyte and granulocyte preparations: a comparative study. J Lab Clin Med 1974;83:570.
Hurst JK. Myeloperoxidase: active site structure and catalytic mechanisms. In: Everse J, Everse KE, Grisham MB, eds. Peroxidases in chemistry and biology, vol. 1. Boca Raton: CRC Press; 1991:37–62.
Wilson DL, Manery JF. The permeability of rabbit leucocytes to sodium, potassium and chloride. J Cell Comp Physiol 1949;34:493.
Thomas L, Aune TM. Cofactor role of iodide in peroxidase antimicrobial action againstEscherichia coli. Antimicrob Agents Chemother 1994;13:1000.
Hermann M, Gmeiner B. Altered susceptibility to in vitro oxidation of LDL and LDL complexes and LDL aggregates. Ann N Y Acad Sci 1993;683:363.
Kostner GM, Laggner P. Chemical and physical properties of lipoproteins. In: Fruchart JC, Shepherd J, eds. Human plasma lipoproteins. Berlin: de Gruyter; 1989:23–54.
Smith EB, Staples EM. Distribution of plasma proteins across the human aortic wall — barrier functions of endothelium and internal elastic lamina. Atherosclerosis 1980;37:579.
Martin WJ II. Neutrophils kill pulmonary endothelial cells by a hydrogen-peroxide-dependent pathway. Am Rev Respir Dis 1984;130:209.
Leake DS. Does an acidic pH explain why low density lipoprotein is oxidised in atherosclerotic lesions? Atherosclerosis 1997;129:149.
Edwards SW, ed. Biochemistry and physiology of the neutrophil. Cambridge: Cambridge University Press, 1994.
Sepe SM, Clark RA. Oxidant membrane injury by the neutrophil myeloperoxidase system. I. Characterization of a liposome model and injury by myeloperoxidase. J Immunol 1985;134:1888.
Hazen SL, Hsu FH, Duffin K, Heinecke JW. Molecular chlorine generated by the myeloperoxidase-hydrogen peroxide-chloride system of phagocytes converts low density lipoprotein cholesterol into a family of chlorinated sterols. J Biol Chem 1996;271:23080.
Kettle AJ, Winterbourn CC. Influence of superoxide on myeloperoxidase kinetics measured with a hydrogen peroxide electrode. Biochem J 1989;263:823.
O’Connell A, Gieseg SP, Stanley KK. Hypochlorite oxidation causes cross-linking of Lp (a). Biochim Biophys Acta 1994;1225:180.
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A. Jerlich and L. Horakova contributed equally to this work.
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Jerlich, A., Horakova, L., Fabjan, J.S. et al. Correlation of low-density lipoprotein modification by myeloperoxidase with hypochlorous acid formation. Int J Clin Lab Res 29, 155–161 (1999). https://doi.org/10.1007/s005990050083
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DOI: https://doi.org/10.1007/s005990050083