Abstract
Oxidant generation is implicated as a major contributor to aging and the degenerative diseases of the aging process (1,2). However, the physiologically relevant mechanisms for oxidative damage have not yet been identified. A potential pathway involves activated phagocytic white blood which employ a membrane-associated NADPH oxidase to generate superoxide (3,4). Superoxide spontaneously or enzymatically dismutates to form hydrogen peroxide. In vitro studies suggest that hydrogen peroxide alone is a relatively unreactive oxidant. However, the oxidative potential of hydrogen peroxide is amplified by myeloperoxidase, a secreted heme protein (3,4). The enzyme represents an attractive candidate for monitoring phagocyte-mediated damage because it generates several distinct oxidants that covalently modify cellular targets.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Stadtman, E. R. (1992) Protein oxidation and aging, Science 257, 1220–1224.
Ames, B. N., Shigenaga, M. K., and Hagen, T. M. (1993) Oxidants, antioxidants, and the degenerative diseases of aging, Proc. Natl. Acad. Sci. 90, 7915–7922.
Klebanoff, S. J. (1980) Oxygen metabolism and the toxic properties of phagocytes, Ann. Intern. Med. 93, 480–489.
Hurst, J. K. and Barrette Jr., W. C. (1989) Leukocytic oxygen activation and microbicidal oxidative toxins, CRC Crit Rev Biochem Mol Biol 24, 271–328.
Berliner, J. A. and Heinecke, J. W. (1996) The role of oxidized lipoproteins in atherogenesis, Free Rad. Biol. Med. 20: 707–727.
Rosenfeld, M. E., Palinski, W.,Ylaherttuala, S., Butler, S. and Witztum, J. L. (1990). Distribution of oxidation specific lipid-protein adducts and apolipoprotein-B in atherosclerotic lesions of varying severity from WHHL rabbits, Arterioscler. 10, 336–349.
Steinberg, D. (1995) Clinical trials of antioxidants in atherosclerosis: Are we doing the right thing? Lancet 346, 36–38.
Stephens, N. G., Parsons, A., Schofield, P. M.,Kelly, F., Cheeseman, K., Mitchinson, M. J. and Brown, M. J. (1996) Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS), Lancet 347, 781–786.
Nauseef, W. M. (1988) Myeloperoxidase deficiency–phagocytic defects I: Abnormalities outside of the respiratory burst, Hematology/Oncology Clinics of North America 2, 135–158.
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. Inv. 94, 437–444.
Harrison, J. E. and Schultz, J. (1976) Studies on the chlorinating activity of myeloperoxidase, J. Biol. Chem. 251, 1371–1374.
Thomas, E. L., Grisham, M. B. and Jefferson, M. M. (1986) Preparation and characterization of chloramines, Meth. in Enzymol. 132, 569–585.
Prince, R. C. (1988) Tyrosine radicals, Trends Biochem. Sci. 13, 286–288.
Anderson, S. O. (1966) Covalent cross-links in a structural protein, Resilin, Acta. Physiol. Scand. 66: 1–81.
Heinecke, J. W., Li, W., Daehnke, H. L.,. III and Goldstein, J. A. (1993) 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.
Heinecke, J. W., Li, W., Francis, G. A. and Goldstein, J. A. (1993) Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative crosslinking of proteins, J. Clin. Invest. 91, 2866–2872.
Francis, G. A., Mendez, A. J., Bierman E. L., and Heinecke, J. W. (1993) Oxidative tyrosylation of high density lipoprotein by peroxidase enhances cholesterol removal from cultured fibroblasts and macrophage foam cells, Proc. Natl. Acad. Sci. 90, 6631–6635.
Savenkova, M. I., 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.
Sepe, S. M. and Clark, R. A. (1985) Oxidant membrane injury by the neutrophil myeloperoxidase system II, J. Immunol. 134, 1896–1901.
VandenBerg, J. J. M., Winterboum, C. C. and Kuypers, F. A. (1993) Hypochlorous acid-mediated modification of cholesterol and phospholipid, J. Lipid Res. 34, 2005–2012.
Heinecke, J. W., Li, W., Mueller, D. M., Bohrer, A. and Turk, J. (1994) Cholesterol chlorohydrin synthesis by the myeloperoxidase-hydrogen peroxide-chloride system: Potential markers for lipoproteins oxidatively damaged by phagocytes. Biochem. 33, 10127–10136.
Hazen, S. L., Hsu, F. F., Duffin, K. and Heinecke, J. W. (1996) 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.,in press.
Hazell, L. J., VandenBerg, 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 by lipid oxidation, Biochem. J. 302, 297–304.
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. Inv. 97, 1535–1544.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Heinecke, J.W. (1997). Molecular Pathology of Oxidative Damage Induced by the Myeloperoxidase System of Activated Phagocytes. In: Minisci, F. (eds) Free Radicals in Biology and Environment. NATO ASI Series, vol 27. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-1607-9_19
Download citation
DOI: https://doi.org/10.1007/978-94-017-1607-9_19
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-4831-8
Online ISBN: 978-94-017-1607-9
eBook Packages: Springer Book Archive