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. 1986 Oct 1;239(1):169–173. doi: 10.1042/bj2390169

Superoxide-dependent and -independent mechanisms of iron mobilization from ferritin by xanthine oxidase. Implications for oxygen-free-radical-induced tissue destruction during ischaemia and inflammation.

P Biemond, A J Swaak, C M Beindorff, J F Koster
PMCID: PMC1147255  PMID: 3026367

Abstract

Xanthine oxidase is able to mobilize iron from ferritin. This mobilization can be blocked by 70% by superoxide dismutase, indicating that part of its action is mediated by superoxide (O2-). Uric acid induced the release of ferritin iron at concentrations normally found in serum. The O2(-)-independent mobilization of ferritin iron by xanthine oxidase cannot be attributed to uric acid, because uricase did not influence the O2(-)-independent part and acetaldehyde, a substrate for xanthine oxidase, also revealed an O2(-)-independent part, although no uric acid was produced. Presumably the amount of uric acid produced by xanthine oxidase and xanthine is insufficient to release a measurable amount of iron from ferritin. The liberation of iron from ferritin by xanthine oxidase has important consequences in ischaemia and inflammation. In these circumstances xanthine oxidase, formed from xanthine dehydrogenase, will stimulate the formation of a non-protein-bound iron pool, and the O2(-)-produced by xanthine oxidase, or granulocytes, will be converted by 'free' iron into much more highly toxic oxygen species such as hydroxyl radicals (OH.), exacerbating the tissue damage.

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Selected References

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

  1. Ames B. N., Cathcart R., Schwiers E., Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6858–6862. doi: 10.1073/pnas.78.11.6858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baldwin D. A., Jenny E. R., Aisen P. The effect of human serum transferrin and milk lactoferrin on hydroxyl radical formation from superoxide and hydrogen peroxide. J Biol Chem. 1984 Nov 10;259(21):13391–13394. [PubMed] [Google Scholar]
  3. Battelli M. G., Corte E. D., Stirpe F. Xanthine oxidase type D (dehydrogenase) in the intestine and other organs of the rat. Biochem J. 1972 Feb;126(3):747–749. doi: 10.1042/bj1260747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Biemond P., van Eijk H. G., Swaak A. J., Koster J. F. Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseases. J Clin Invest. 1984 Jun;73(6):1576–1579. doi: 10.1172/JCI111364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carlin G., Djursäter R. Xanthine oxidase induced depolymerization of hyaluronic acid in the presence of ferritin. FEBS Lett. 1984 Nov 5;177(1):27–30. doi: 10.1016/0014-5793(84)80974-6. [DOI] [PubMed] [Google Scholar]
  6. Chambers D. E., Parks D. A., Patterson G., Roy R., McCord J. M., Yoshida S., Parmley L. F., Downey J. M. Xanthine oxidase as a source of free radical damage in myocardial ischemia. J Mol Cell Cardiol. 1985 Feb;17(2):145–152. doi: 10.1016/s0022-2828(85)80017-1. [DOI] [PubMed] [Google Scholar]
  7. Crichton R. R. Structure and function of ferritin. Angew Chem Int Ed Engl. 1973;12(1):57–65. doi: 10.1002/anie.197300571. [DOI] [PubMed] [Google Scholar]
  8. Crowell J. W., Jones C. E., Smith E. E. Effect of allopurinol on hemorrhagic shock. Am J Physiol. 1969 Apr;216(4):744–748. doi: 10.1152/ajplegacy.1969.216.4.744. [DOI] [PubMed] [Google Scholar]
  9. DeWall R. A., Vasko K. A., Stanley E. L., Kezdi P. Responses of the ischemic myocardium to allopurinol. Am Heart J. 1971 Sep;82(3):362–370. doi: 10.1016/0002-8703(71)90302-4. [DOI] [PubMed] [Google Scholar]
  10. Duggan D. E., Streeter K. B. Inhibition of ferritin reduction by pyrazolo(3,4d)pyrimidines. Arch Biochem Biophys. 1973 May;156(1):66–70. doi: 10.1016/0003-9861(73)90341-x. [DOI] [PubMed] [Google Scholar]
  11. GREEN S., MAZUR A. Relation of uric acid metabolism to release of iron from hepatic ferritin. J Biol Chem. 1957 Aug;227(2):652–668. [PubMed] [Google Scholar]
  12. Graf E., Mahoney J. R., Bryant R. G., Eaton J. W. Iron-catalyzed hydroxyl radical formation. Stringent requirement for free iron coordination site. J Biol Chem. 1984 Mar 25;259(6):3620–3624. [PubMed] [Google Scholar]
  13. Granger D. N., Rutili G., McCord J. M. Superoxide radicals in feline intestinal ischemia. Gastroenterology. 1981 Jul;81(1):22–29. [PubMed] [Google Scholar]
  14. Gutteridge J. M., Halliwell B., Treffry A., Harrison P. M., Blake D. Effect of ferritin-containing fractions with different iron loading on lipid peroxidation. Biochem J. 1983 Feb 1;209(2):557–560. doi: 10.1042/bj2090557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gutteridge J. M., Rowley D. A., Halliwell B. Superoxide-dependent formation of hydroxyl radicals in the presence of iron salts. Detection of 'free' iron in biological systems by using bleomycin-dependent degradation of DNA. Biochem J. 1981 Oct 1;199(1):263–265. doi: 10.1042/bj1990263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Halliwell B., Gutteridge J. M. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J. 1984 Apr 1;219(1):1–14. doi: 10.1042/bj2190001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Harrison P. M. Ferritin: an iron-storage molecule. Semin Hematol. 1977 Jan;14(1):55–70. [PubMed] [Google Scholar]
  18. KINNEY T. D., KAUFMAN N., KLAVINS J. V. Xanthine oxidas activity and iron storage in the liver. Proc Soc Exp Biol Med. 1961 Oct;108:22–24. doi: 10.3181/00379727-108-26833. [DOI] [PubMed] [Google Scholar]
  19. Koster J. F., Slee R. G. Lipid peroxidation of human erythrocyte ghosts induced by organic hydroperoxides. Biochim Biophys Acta. 1983 Jul 12;752(2):233–239. doi: 10.1016/0005-2760(83)90117-0. [DOI] [PubMed] [Google Scholar]
  20. Kozma C., Salvador R. A., Elion G. B. Chronic allopurinol administration and iron storage in mice. Life Sci. 1968 Apr 1;7(7):341–348. doi: 10.1016/0024-3205(68)90002-7. [DOI] [PubMed] [Google Scholar]
  21. Krenitsky T. A., Tuttle J. V., Cattau E. L., Jr, Wang P. A comparison of the distribution and electron acceptor specificities of xanthine oxidase and aldehyde oxidase. Comp Biochem Physiol B. 1974 Dec 15;49(4):687–703. doi: 10.1016/0305-0491(74)90256-9. [DOI] [PubMed] [Google Scholar]
  22. MAZUR A., BAEZ S., SHORR E. The mechanism of iron release from ferritin as related to its biological properties. J Biol Chem. 1955 Mar;213(1):147–160. [PubMed] [Google Scholar]
  23. MAZUR A., CARLETON A. HEPATIC XANTHINE OXIDASE AND FERRITIN IRON IN THE DEVELOPING RAT. Blood. 1965 Sep;26:317–322. [PubMed] [Google Scholar]
  24. MAZUR A., GREEN S., SAHA A., CARLETON A. Mechanism of release of ferritin iron in vivo by xanthine oxidase. J Clin Invest. 1958 Dec;37(12):1809–1817. doi: 10.1172/JCI103774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Massey V., Brumby P. E., Komai H. Studies on milk xanthine oxidase. Some spectral and kinetic properties. J Biol Chem. 1969 Apr 10;244(7):1682–1691. [PubMed] [Google Scholar]
  26. McCord J. M., Fridovich I. The reduction of cytochrome c by milk xanthine oxidase. J Biol Chem. 1968 Nov 10;243(21):5753–5760. [PubMed] [Google Scholar]
  27. McCord J. M. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med. 1985 Jan 17;312(3):159–163. doi: 10.1056/NEJM198501173120305. [DOI] [PubMed] [Google Scholar]
  28. McCord J. M., Roy R. S. The pathophysiology of superoxide: roles in inflammation and ischemia. Can J Physiol Pharmacol. 1982 Nov;60(11):1346–1352. doi: 10.1139/y82-201. [DOI] [PubMed] [Google Scholar]
  29. Powell L. W., Emmerson B. T. Haemosiderosis associated with xanthine oxidase inhibition. Lancet. 1966 Jan 29;1(7431):239–240. doi: 10.1016/s0140-6736(66)90056-0. [DOI] [PubMed] [Google Scholar]
  30. Romson J. L., Hook B. G., Kunkel S. L., Abrams G. D., Schork M. A., Lucchesi B. R. Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation. 1983 May;67(5):1016–1023. doi: 10.1161/01.cir.67.5.1016. [DOI] [PubMed] [Google Scholar]
  31. Thomas C. E., Morehouse L. A., Aust S. D. Ferritin and superoxide-dependent lipid peroxidation. J Biol Chem. 1985 Mar 25;260(6):3275–3280. [PubMed] [Google Scholar]
  32. Topham R. W., Walker M. C., Calisch M. P. Liver xanthine dehydrogenase and iron mobilization. Biochem Biophys Res Commun. 1982 Dec 31;109(4):1240–1246. doi: 10.1016/0006-291x(82)91910-6. [DOI] [PubMed] [Google Scholar]
  33. Wills E. D. Mechanisms of lipid peroxide formation in animal tissues. Biochem J. 1966 Jun;99(3):667–676. doi: 10.1042/bj0990667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Winterbourn C. C. Lactoferrin-catalysed hydroxyl radical production. Additional requirement for a chelating agent. Biochem J. 1983 Jan 15;210(1):15–19. doi: 10.1042/bj2100015. [DOI] [PMC free article] [PubMed] [Google Scholar]

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