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. 1987 Apr 1;243(1):55–59. doi: 10.1042/bj2430055

Release of iron from ferritin by xanthine oxidase. Role of the superoxide radical.

B J Bolann, R J Ulvik
PMCID: PMC1147813  PMID: 3038086

Abstract

Mobilization of iron from ferritin by xanthine oxidase was studied under aerobic and anaerobic conditions. Aerobic iron release amounted to approx. 3.7 nmol/ml in 10 min. This amount was decreased by approx. 30% under anaerobic conditions. Aerobic iron mobilization involved two mechanisms. About 70% was released by O2.- generated by xanthine oxidase. The rest was released by O2(.-)-independent mechanisms, which also accounted for the total iron release when O2 was absent. A possible transfer of reducing equivalents directly from xanthine oxidase to ferritin is discussed. The results imply that, in pathological conditions with increased formation of O2.-, iron may be released from ferritin. Furthermore, in hypoxic tissues xanthine oxidase can release iron from ferritin by an O2(.-)-independent process. Free iron is liable to catalyse the formation of the extremely reactive and damaging OH. radical.

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Selected References

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  1. Babior B. M. The respiratory burst of phagocytes. J Clin Invest. 1984 Mar;73(3):599–601. doi: 10.1172/JCI111249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  4. Cadenas E., Sies H. Low-level chemiluminescence as an indicator of singlet molecular oxygen in biological systems. Methods Enzymol. 1984;105:221–231. doi: 10.1016/s0076-6879(84)05029-1. [DOI] [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. 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]
  7. Ford G. C., Harrison P. M., Rice D. W., Smith J. M., Treffry A., White J. L., Yariv J. Ferritin: design and formation of an iron-storage molecule. Philos Trans R Soc Lond B Biol Sci. 1984 Feb 13;304(1121):551–565. doi: 10.1098/rstb.1984.0046. [DOI] [PubMed] [Google Scholar]
  8. Grace N. D., Greenwald M. A., Greenberg M. S. Effect of allopurinol on iron mobilization. Gastroenterology. 1970 Jul;59(1):103–108. [PubMed] [Google Scholar]
  9. 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]
  10. Halliwell B., Gutteridge J. M. Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Arch Biochem Biophys. 1986 May 1;246(2):501–514. doi: 10.1016/0003-9861(86)90305-x. [DOI] [PubMed] [Google Scholar]
  11. Hochstein P., Hatch L., Sevanian A. Uric acid: functions and determination. Methods Enzymol. 1984;105:162–166. doi: 10.1016/s0076-6879(84)05022-9. [DOI] [PubMed] [Google Scholar]
  12. Jacobs A. An intracellular transit iron pool. Ciba Found Symp. 1976 Dec 7;(51):91–106. doi: 10.1002/9780470720325.ch5. [DOI] [PubMed] [Google Scholar]
  13. Jones T., Spencer R., Walsh C. Mechanism and kinetics of iron release from ferritin by dihydroflavins and dihydroflavin analogues. Biochemistry. 1978 Sep 19;17(19):4011–4017. doi: 10.1021/bi00612a021. [DOI] [PubMed] [Google Scholar]
  14. Koster J. F., Slee R. G. Ferritin, a physiological iron donor for microsomal lipid peroxidation. FEBS Lett. 1986 Apr 7;199(1):85–88. doi: 10.1016/0014-5793(86)81228-5. [DOI] [PubMed] [Google Scholar]
  15. MARGOLIASH E., FROHWIRT N. Spectrum of horse-heart cytochrome c. Biochem J. 1959 Mar;71(3):570–572. doi: 10.1042/bj0710570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. McCord J. M., Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049–6055. [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Nagano T., Fridovich I. Does the aerobic xanthine oxidase reaction generate singlet oxygen? Photochem Photobiol. 1985 Jan;41(1):33–37. doi: 10.1111/j.1751-1097.1985.tb03444.x. [DOI] [PubMed] [Google Scholar]
  21. O'Connell M. J., Ward R. J., Baum H., Peters T. J. The role of iron in ferritin- and haemosiderin-mediated lipid peroxidation in liposomes. Biochem J. 1985 Jul 1;229(1):135–139. doi: 10.1042/bj2290135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schacter L. P. Measurement of free radical oxygen generation by cytochrome c reduction requirement for cytochrome c oxidase blockade. Biochem Biophys Res Commun. 1985 Feb 28;127(1):354–357. doi: 10.1016/s0006-291x(85)80166-2. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Topham R. W., Jackson M. R., Joslin S. A., Walker M. C. Studies of the ferroxidase activity of native and chemically modified xanthine oxidoreductase. Biochem J. 1986 Apr 1;235(1):39–44. doi: 10.1042/bj2350039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Ulvik R., Romslo I. Studies on the mobilization of iron from ferritin by isolated rat liver mitochondria. Biochim Biophys Acta. 1979 Dec 3;588(2):256–271. doi: 10.1016/0304-4165(79)90209-5. [DOI] [PubMed] [Google Scholar]
  27. Ulvik R., Romslo I. Studies on the utilization of ferritin iron in the ferrochelatase reaction of isolated rat liver mitochondria. Biochim Biophys Acta. 1978 Jun 15;541(2):251–262. doi: 10.1016/0304-4165(78)90398-7. [DOI] [PubMed] [Google Scholar]
  28. Watt G. D., Frankel R. B., Papaefthymiou G. C. Reduction of mammalian ferritin. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3640–3643. doi: 10.1073/pnas.82.11.3640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. White B. C., Krause G. S., Aust S. D., Eyster G. E. Postischemic tissue injury by iron-mediated free radical lipid peroxidation. Ann Emerg Med. 1985 Aug;14(8):804–809. doi: 10.1016/s0196-0644(85)80062-7. [DOI] [PubMed] [Google Scholar]
  30. Williams D. M., Lee G. R., Cartwright G. E. The role of superoxide anion radical in the reduction of ferritin iron by xanthine oxidase. J Clin Invest. 1974 Feb;53(2):665–667. doi: 10.1172/JCI107603. [DOI] [PMC free article] [PubMed] [Google Scholar]

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