Abstract
It has been well established that the actual toxicity of free radical oxygen-species is dependent on the presence of catalytic amounts of free iron in the tissue. Accumulating evidence is present, indicating that for the myocardial tissue damage occurring during reperfusion after ischemic period, oxygen free radicals are partially responsible. It has been demonstrated that superoxide dismutase decreased the ischemic-induced tissue damage. Based on the hypothesis of McCord and coworkers, implying the conversion of heart tissue xanthine dehydrogenase (XDH) to xanthine oxidase (XO) during ischemia and subsequent superoxide (O -2 ) formation during the conversion of the ATP breakdown product(s) (hypo)xanthine to urate, we studied whether XO is able to mobilize free iron from the iron-binding protein ferritin and transferrin. It appeared that XO-mediated O -2 formation is able to release free iron from the intracellular ferritin, but not from extracellular transferrin. Beside this O -2 -dependent iron release and O -2 -independent Fe mobilization could be demonstrated. The latter phenomenon indicates that during the anoxic/ischemic period iron is mobilized from the ferritin. During myocardial reperfusion when XHD is converted to XO and ATP breakdown happens, the previous released iron starts catalyzing the formation of the most potent oxygen free radical, OH- (hydroxyl radical).
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References
Bannister, J.V., Bannister, W.H. and Thornalley, P.J. (1984). The effect of ferritin iron loading on hydroxyl radical production. Live Chem. Rep. S2: 64–72.
Biemond, P., van Eijk, H.G., Swaak, A.J.G. and Koster, J.F. (1984). Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leucocytes. Possible mechanism in inflammation disease. J. Clin. Invest. 73: 1576–1579.
Biemond, P., Swaak, A.J.G., Beindorff, C.M. and Koster, J.F. (1986). Superoxide-dependent and independent mechanism of iron mobilization from ferritin by xanthine oxidase. Biochem. J. 239: 169–173
Carlin, J. and Djursater, R. (1984). Xanthine oxidase induced depolymerization of Hyalunoric acid in the presence of ferritin. FEBS Letters, 177: 27–30.
Carlin, G and Asford, K.E. (1985). Peroxidation of liposomes promoted by human polymorphonuclear cells leucocytes. J. Free Rad. Biol. Med. 1: 437–442.
Fridovich, I. (1979). Hypoxia and oxygen toxicity. Adv. Neurology 26: 255–259.
Gerlach, E., Nees, S. and Becker, B.F. (1985). The vascular endothelium: a servey of some newly evolving biochemical and physiological features. Basic Res. Cardiol. 80: 459–474.
Guarnieri, C., Flamigni, F. and Caldarara, C.M. (1980). Role of oxygen in the cellular damage induced by re-oxygenation of hypoxic heart. J. Mol. Cell. Cardiol., 12: 797–808.
Gutteridge, J.M.C., Rowley, D.A. and Halliwell, B. (1981). Superoxide-dependent formation of hydroxyl radicals in the presence of iron salts. Detection of “free” iron in biological systems by using bleomycine dependent degradation of DNA. Biochem. J. 199: 263–265.
Gutteridge, J.M.C., Halliwell, B., Treffry, A., Harrison, P.M. and Blake, D. (1983). Effect of ferritin-containing fractions with different iron loading on lipid peroxidation. Biochem. J. 209: 557–560.
Hall, E.T. (1977). The oxygen effect, in E.T. Hall (editor). pp. 48.
Halliwell, B. (1979). Superoxide-dependent formation of hydroxyl radicals in the presence of iron chelates. FEBS Letters, 92: 321–326.
Harrison, P.M. (1979). Ferritin: an iron storage protein. Semin. Hematol., 14: 55–70.
Jolly, S.R., Kane, W.J., Baillie, M.B., Abrams, G.D. and Lucchesi, B.R. (1984). Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase. Circ. Res. 54: 277–285.
Julicher, R.H.M., Tuburg, L.B.M., Sterrenberg, L., Bast, A., Koomen, J.M. and Noordhoek, J. (1984). Decreased defence against free radicals in rat heart during normal perfusion after hypoxic, ischemic and calcium-free perfusion. Life Sci. 35: 1281–1288.
Koster, J.F. and Slee, R.G. (1986). Ferritin, a physiological iron donor for microsomal lipid peroxidation. FEBS Letters, 199: 85–89.
Koster, J.F., Slee, R.G. and Stam, H. (1985). Studies on cumene hydroperoxide-induced lipid peroxidation in the isolated heart. J. Moll. Cell. Card. 17: 701–708.
Mazur, A., Baez, S., and Shorr, E., (1955). The mechanism of iron release from ferritin as related to its biological properties. J. Biol. Chem. 213: 147–160.
Mazur, A., Green, S., Saha, A. and Carleton, A. (1958). Mechanism of release of ferritin iron in vivo by xanthine oxidase. J. Clin. Invest. 37: 1809–1817.
McCord, J.M. and Roy, R.S. (1982). Pathophysiology of superoxide: Roles in inflammation and ischemia. Can. J. Physiol. 60: 1346–1352.
Meerson, F.Z., Kagan, V.E., Kozlov, Y.P., Belkina, L.M. and Arkhipanko, V. (1982). The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart.
O’Connell, M.J., Ward, R.J., Baum, H. and Peters, T.J. (1985). The role of iron in ferritin and haemosiderin mediated lipid peroxidation of liposomes. Biochem. J., 229: 135–139.
O’Connell, M.J., Halliwell, B., Moorhouse, C.P., Aruoma, O.I., Baum, H. and Peters, T.J. (1986). Formation of hydroxyl radicals in the presence of ferritin and haemosiderin. Is haemosiderin formation a biological protective mechanism? Biochem. J., 234: 727–731.
Piper, H.M., Spahr, R., Hütter, J.F. and Spieckermann, P.G. (1985). The calcium and the oxygen paradox: non existent on the cellar level. Basic Res. Cardiol. 80; Suppl 2: 159–163.
Shingu, M., Yoshioka, M., Nobunoga, M and Yoshida, K. (1985). Human vascular smooth muscle cells and endothelial cells lack catalase activity and are susceptible to hydrogen peroxide. Inflammation, 9: 309–320.
Stam, H. and Koster, J.F. (1985). Fatty acid peroxidation is ischemia. In: Schrör(editor), Prostaglandines and other Eicosanoïds in the cardiovascular system, pp 131–148.
Thomas, C.E., Morehouse, L.A. and Aust, S.D. (1985). Ferritin and superoxide-dependent lipid peroxidation. J. Biol. Chem. 260: 3275–3280.
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© 1988 ECSC, EEC, EAEC, Brussels and Luxembourg
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Koster, J.F., Stam, H., Biemond, P. (1988). The Role of Iron Mobilization in Ischemic Tissue Damage. In: L’Abbate, A., Ursini, F. (eds) The Role of Oxygen Radicals in Cardiovascular Diseases. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-2697-4_10
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DOI: https://doi.org/10.1007/978-94-009-2697-4_10
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