Advertisement

Biometals

, Volume 19, Issue 3, pp 323–333 | Cite as

Ascorbate-mediated Iron Release from Ferritin in the Presence of Alloxan

  • Koichi Sakurai
  • Ami Nabeyama
  • Yukio Fujimoto
Article

Abstract

Release of iron from ferritin requires reduction of ferric to ferrous iron. The iron can participate in the diabetogenic action of alloxan. We investigated the ability of ascorbate to catalyze the release of iron from ferritin in the presence of alloxan. Incubation of ferritin with ascorbate alone elicited iron release (33 nmol/10 min) and the generation of ascorbate free radical, suggesting a direct role for ascorbate in iron reduction. Iron release by ascorbate significantly increased in the presence of alloxan, but alloxan alone was unable to release measurable amounts of iron from ferritin. Superoxide dismutase significantly inhibited ascorbate-mediated iron release in the presence of alloxan, whereas catalase did not. The amount of alloxan radical (A·) generated in reaction systems containing both ascorbate and alloxan decreased significantly upon addition of ferritin, suggesting that A· is directly involved in iron reduction. Although release of iron from ferritin and generation of A· were also observed in reactions containing GSH and alloxan, the amount of iron released in these reactions was not totally dependent on the amount of A· present, suggesting that other reductants in addition to A· (such as dialuric acid) may be involved in iron release mediated by GSH and alloxan. These results suggest that A· is the main reductant involved in ascorbate-mediated iron release from ferritin in the presence of alloxan and that both dialuric acid and A· contribute to GSH/alloxan-mediated iron release.

Keywords

ascorbate ferritin alloxan alloxan radical glutathione 

Abbreviations

Alloxan radical

AFR

Ascorbate free radical

BPS

bathophenanthrolinedisulfonic acid disodium salt

EDTA

ethylenediaminetetraacetic acid

ESR

electron spin resonance

GSH

glutathione reduced form

2

superoxide anion radical

PBS

phosphate buffered saline

ROS

reactive oxygen species

SOD

superoxide dismutase

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bienfait, HF, Briel, ML 1980Rapid mobilization of ferritin iron by ascorbate in the presence of oxygenBiochim Biophys Acta631507510PubMedGoogle Scholar
  2. Biemond, P, Eijk, HG, Swaak, AJG, Koster, JF 1984Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseasesJ Clin Invest7315761579PubMedCrossRefGoogle Scholar
  3. Bonomi, F, Pagani, S 1986Removal of ferritin-bound iron by DL-dihydrolipoate and DL-dihydrolipoamideEur J Biochem155295300PubMedCrossRefGoogle Scholar
  4. Boyer, RF, McCleary, CJ 1987Superoxide ion as a primary reductant in ascorbate-mediated ferritin iron releaseFree Radic Biol Med3389395PubMedCrossRefGoogle Scholar
  5. Bromme, HJ, Weinandy, R, Peschke, D, Peschke, E 2001Simultaneous quantitative determination of alloxan, GSH and GSSG by HPLC. Estimation of the frequency of redox cycling between alloxan and dialuric acidHorm Metab Res33106109PubMedCrossRefGoogle Scholar
  6. Cassanelli, A, Moulis, JM 2001Sulfide is an efficient iron releasing agent for mammalian ferritinsBiochim Biophys Acta1547174182PubMedGoogle Scholar
  7. Cederbaum, AI 1992Iron and ethanol-induced tissue damage: Generation of reactive oxygen intermediates and possible mechanism for their role in alcohol liver toxicityLauffer, RB eds. Iron and Human DiseaseCRC pressBoca Raton419447Google Scholar
  8. Egana, JT, Zambrano, C, Nunez, MT, Gonzalez-Billault, C, Maccioni, RB 2003Iron-induced oxidative stress modify tau phosphorylation patterns in hippocampal cell culturesBiometals16215223PubMedCrossRefGoogle Scholar
  9. El-Hage, AN, Herman, EH, Yang, GC, Crouch, RK, Ferrans, VJ 1986Mechanism of the protective activity of ICRF-187 against alloxan-induced diabetes in miceRes Commun Chem Pathol Pharmacol52341360PubMedGoogle Scholar
  10. Fischer, LJ, Hamburger, SA 1980Inhibition of alloxan action in isolated pancreatic islets by superoxide dismutase, catalase, and a metal chelatorDiabetes29213216PubMedGoogle Scholar
  11. Halliwell, B, Gutteridge, JMC 1984Oxygen toxicity, oxygen radicals, transition metals and diseaseBiochem J219114PubMedGoogle Scholar
  12. Harrison, PM, Hoare, RJ, Hoy, TG, Macara, IG 1974Mobilization of Ferritin ironJacobs, AWorwood, M eds. Iron in biochemistry and medicineAcademic PressLondon and New York104106Google Scholar
  13. Johnson Inbaraj, J, Gandhidasan, R, Murugesan, R 1999Cytotoxicity and superoxide anion generation by some naturally occurring quinonesFree Radic Biol Med2610721078PubMedCrossRefGoogle Scholar
  14. Jones, T, Spencer, R, Walsh, C 1978Mechanism and kinetics of iron release from ferritin by dihydroflavins and dihydroflavin analoguesBiochemistry1740114017PubMedCrossRefGoogle Scholar
  15. Katoh, M, Sakurai, K, Fujimoto, Y 2002Alloxan radical- induced generation of reactive oxygen species in the reaction system of alloxan with ascorbateYakugaku Zasshi122831839PubMedCrossRefGoogle Scholar
  16. Lovstad, RA 2003A kinetic study on iron stimulation of the xanthine oxidase dependent oxidation of ascorbateBiometals16435439PubMedCrossRefGoogle Scholar
  17. May, JM, Cobb, CE, Mendiratta, S, Hill, KE, Burk, RF 1998Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductaseJ Biol Chem2732303923045PubMedCrossRefGoogle Scholar
  18. Miura, T, Sakurai, K 1988Iron release from ferritin by alloxan radicalLife Sci4321452149PubMedCrossRefGoogle Scholar
  19. Oberley, LW 1988Free radicals and diabetesFree Radic Biol Med5113134PubMedCrossRefGoogle Scholar
  20. Prior, RL, Cao, G 1999In vivo total antioxidant capacity: comparison of different analytical methodsFree Radic Biol Med2711731181PubMedCrossRefGoogle Scholar
  21. Reif, DW 1992Ferritin as a source of iron for oxidative damageFree Radic Biol Med12417427PubMedCrossRefGoogle Scholar
  22. Reif, DW, Samokyszyn, VM, Miller, DM, Aust, SD 1989Alloxan- and glutathione-dependent ferritin iron release and lipid peroxidationArch Biochem Biophys269407414PubMedCrossRefGoogle Scholar
  23. Sakurai, K, Katoh, M, Someno, K, Fujimoto, Y 2001Apoptosis and mitochondrial damage in INS-1 cells treated with alloxanBiol Pharm Bull24876882PubMedCrossRefGoogle Scholar
  24. Sakurai, K, Haga, K, Ogiso, T 1994A role of iron in lambda DNA strand breaks in the reaction system of alloxan with reduced glutathione: iron(III) binding to the DNABiol Pharm Bull17227231PubMedGoogle Scholar
  25. Sakurai, K, Cederbaum, AI 1998Oxidative stress and cytotoxicity induced by ferric-nitrilotriacetate in HepG2 cells that express cytochrome P450 2E1Mol Pharmacol5410241035PubMedGoogle Scholar
  26. Sakurai, K, Miura, T, Ogiso, T 1990Role of alloxan radical in generation of hydroxyl radical by reaction of alloxan with glutathione in the presence of Fe3+-ethylenediaminetetraacetic acidChem Pharm Bull38993997Google Scholar
  27. Sakurai, K, Ogawa, Y, Miura, T, Ogiso, T 1988Studies on biological damage by active oxygens. II. Inhibition of insulin release from isolated pancreatic islets by exposure to O 2 -generating system of hypoxanthine-xanthine oxidaseYakugaku Zasshi108150155PubMedGoogle Scholar
  28. Sakurai, K, Ogiso, T 1991Inhibitory effect of glutathione on the generation of hydroxyl radicals in the reaction system of glutathione-alloxanChem Pharm Bull39737742Google Scholar
  29. Winterbourn, CC 1982Superoxide dismutase-inhibitible reduction of cytochrome c by the alloxan radicalImplications for alloxan cytotoxicity. Biochem J207609612Google Scholar
  30. Yi, J, Yang, J, He, R, Gao, F, Sang, H, Tang, X, Ye, RD 2004Emodin enhances arsenic trioxide-induced apoptosis via generation of reactive oxygen species and inhibition of survival signalingCancer Res64108116PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  1. 1.Department of BiochemistryHokkaido Pharmaceutical UniversityOtaruJapan

Personalised recommendations