JBIC Journal of Biological Inorganic Chemistry

, Volume 12, Issue 3, pp 345–352

Crucial role of lysosomal iron in the formation of dinitrosyl iron complexes in vivo

  • Hanna Lewandowska
  • Sylwia Męczyńska
  • Barbara Sochanowicz
  • Jarosław Sadło
  • Marcin Kruszewski
Original Paper

Abstract

Dinitrosyl non-heme–iron complexes (DNIC) are found in many nitric oxide producing tissues. A prerequisite of DNIC formation is the presence of nitric oxide, iron and thiol/imidazole groups. The aim of this study was to investigate the role of the cellular labile iron pool in the formation of DNIC in erythroid K562 cells. The cells were treated with a nitric oxide donor in the presence of a permeable (salicylaldehyde isonicotinoyl hydrazone) or a nonpermeable (desferrioxamine mesylate) iron chelator and DNIC formation was recorded using electron paramagnetic resonance. Both chelators inhibited DNIC formation up to 50% after 6 h of treatment. To further investigate the role of lysosomal iron in DNIC formation, we prevented lysosomal proteolysis by pretreatment of whole cells with NH4Cl. Pretreatment with NH4Cl inhibited the formation of DNIC in a time-dependent manner that points to the importance of the degradation of iron metalloproteins in DNIC formation in vivo. Fractionation of the cell content after treatment with the nitric oxide donor revealed that DNIC is formed predominantly in the endosomal/lysosomal fraction. Taken together, these data indicate that lysosomal iron plays a crucial role in DNIC formation in vivo. Degradation of iron-containing metalloproteins seems to be important for this process.

Keywords

K562 cells Electron paramagnetic resonance Nitric oxide Salicylaldehyde isonicotinoyl hydrazone Desferrioxamine mesylate 

Abbreviations

DEANO

2-(N,N-Diethylamino)-diazenolate-2-oxide

DFO

Desferrioxamine mesylate

DNIC

Dinitrosyl non-heme–iron complexes

EPR

Electron paramagnetic resonance

Hepes

N-(2-Hydroxyethyl)piperazine-N′-ethanesulfonic acid

LIP

Labile iron pool

MRP1

Multidrug-resistance-associated protein 1

PBS

Phosphate-buffered saline

SIH

Salicylaldehyde isonicotinoyl hydrazone

References

  1. 1.
    Drapier JC, Pellat C, Henry Y (1991) J Biol Chem 266:10162–10167PubMedGoogle Scholar
  2. 2.
    Bastian NR, Yim CY, Hibbs JB Jr, Samlowski WE (1994) J Biol Chem 269:5127–5131PubMedGoogle Scholar
  3. 3.
    Pieper GM, Halligan NL, Hilton G, Konorev EA, Felix CC, Roza AM, Adams MB, Griffith OW (2003) Proc Natl Acad Sci USA 100:3125–3130PubMedCrossRefGoogle Scholar
  4. 4.
    Pillay CS, Elliott E, Dennison C (2002) Biochem J 363:417–429PubMedCrossRefGoogle Scholar
  5. 5.
    Vanin AF, Malenkova IV, Serezhenkov VA (1997) Nitric Oxide 1:191–203PubMedCrossRefGoogle Scholar
  6. 6.
    Costanzo S, Menage S, Purrello R, Bonomo RP, Fontecave M (2001) Inorg Chim Acta 318:1–7CrossRefGoogle Scholar
  7. 7.
    Vanin A, Kleschyov A (1999) In: Lukiewicz S, Zweier JL (eds) Nitric oxide in transplant rejection and anti-tumor defence. Kluwer, Boston, pp 49–82Google Scholar
  8. 8.
    Ueno T, Yoshimura T (2000) Jpn J Pharmacol 82:95–101PubMedCrossRefGoogle Scholar
  9. 9.
    Vanin AF (1998) Biochemistry (Moscow) 63:782–793Google Scholar
  10. 10.
    Keese MA, Bose M, Mulsch A, Schirmer RH, Becker K (1997) Biochem Pharmacol 54:1307–1313PubMedCrossRefGoogle Scholar
  11. 11.
    Henry Y, Ducrocq C, Drapier JC, Servent D, Pellat C, Guissani A (1991) Eur Biophys J 20:1–15PubMedCrossRefGoogle Scholar
  12. 12.
    Kim YM, Chung HT, Simmons RL, Billiar TR (2000) J Biol Chem 275:10954–10961PubMedCrossRefGoogle Scholar
  13. 13.
    Cesareo E, Parker LJ, Pedersen JZ, Nuccetelli M, Mazzetti AP, Pastore A, Federici G, Caccuri AM, Ricci G, Adams JJ, Parker MW, Bello ML (2005) J Biol Chem 280:42172–42180PubMedCrossRefGoogle Scholar
  14. 14.
    Kruszewski M (2003) Mutation Res 531:81–92PubMedGoogle Scholar
  15. 15.
    Kurz T, Gustafsson B, Brunk UT (2006) FEBS J 273:3106–3117PubMedCrossRefGoogle Scholar
  16. 16.
    Kroemer G, Jaattela M (2005) Nat Rev Cancer 5:886–897PubMedCrossRefGoogle Scholar
  17. 17.
    Klionsky DJ, Emr SD (2000) Science 290:1717–1721PubMedCrossRefGoogle Scholar
  18. 18.
    Cuervo AM, Dice JF (1998) J Mol Med 76:6–12PubMedCrossRefGoogle Scholar
  19. 19.
    Roberts S, Bomford A (1988) J Biol Chem 263:19181–19187PubMedGoogle Scholar
  20. 20.
    Radisky DC, Kaplan J (1998) Biochem J 336(Pt 1):201–205PubMedGoogle Scholar
  21. 21.
    Persson HL, Nilsson KJ, Brunk UT (2001) Redox Rep 6:57–63PubMedCrossRefGoogle Scholar
  22. 22.
    Yu Z, Persson HL, Eaton JW, Brunk UT (2003) Free Radic Biol Med 34:1243–1252PubMedCrossRefGoogle Scholar
  23. 23.
    Tenopoulou M, Doulias PT, Barbouti A, Brunk U, Galaris D (2005) Biochem J 387:703–710PubMedCrossRefGoogle Scholar
  24. 24.
    Persson HL, Kurz T, Eaton JW, Brunk UT (2005) Biochem J 389:877–884PubMedCrossRefGoogle Scholar
  25. 25.
    Zanninelli G, Glickstein H, Breuer W, Milgram P, Brissot P, Hider RC, Konijn AM, Libman J, Shanzer A, Cabantchik ZI (1997) Mol Pharmacol 51:842–852PubMedGoogle Scholar
  26. 26.
    Laub R, Schneider YJ, Octave JN, Trouet A, Crichton RR (1985) Biochem Pharmacol 34:1175–1183PubMedCrossRefGoogle Scholar
  27. 27.
    Cable H, Lloyd JB (1999) J Pharm Pharmacol 51:131–134PubMedCrossRefGoogle Scholar
  28. 28.
    Graham JM (1993) Methods Mol Biol 19:29–40PubMedGoogle Scholar
  29. 29.
    Kennedy MC, Antholine WE, Beinert H (1997) J Biol Chem 272:20340–20347PubMedCrossRefGoogle Scholar
  30. 30.
    Kurz T, Leake A, von Zglinicki T, Brunk UT (2004) Biochem J 378:1039–1045PubMedCrossRefGoogle Scholar
  31. 31.
    de Duve C, de Barsy T, Poole B, Trouet A, Tulkens P, van Hoof F (1974) Biochem Pharmacol 23:2495–2531PubMedCrossRefGoogle Scholar
  32. 32.
    Ignarro LJ (ed.) (2000) Nitric oxide: biology and pathobiology. Academic, San DiegoGoogle Scholar
  33. 33.
    Quintana C, Bellefqih S, Laval JY, Guerquin-Kern JL, Wu TD, Avila J, Ferrer I, Arranz R, Patino C (2006) J Struct Biol 153:42–54PubMedCrossRefGoogle Scholar
  34. 34.
    Bienfait HF, van den Briel ML (1980) Biochim Biophys Acta 631:507–510PubMedGoogle Scholar
  35. 35.
    Funk F, Lenders JP, Crichton RR, Schneider W (1985) Eur J Biochem 152:167–172PubMedCrossRefGoogle Scholar
  36. 36.
    Bolann BJ, Ulvik RJ (1987) Biochem J 243:55–59PubMedGoogle Scholar
  37. 37.
    Hernandez-Yago J, Knecht E, Martinez-Ramon A, Grisolia S (1980) Cell Tissue Res 205:303–309PubMedCrossRefGoogle Scholar
  38. 38.
    Konijn AM, Glickstein H, Vaisman B, Meyron-Holtz EG, Slotki IN, Cabantchik ZI (1999) Blood 94:2128–2134PubMedGoogle Scholar
  39. 39.
    Abouhamed M, Gburek J, Liu W, Torchalski B, Wilhelm A, Wolff NA, Christensen EI, Thevenod F, Smith CP (2006) Am J Physiol Renal Physiol 290:F1525–F1533PubMedCrossRefGoogle Scholar
  40. 40.
    Gruper Y, Bar J, Bacharach E, Ehrlich R (2005) J Cell Physiol 204:901–912PubMedCrossRefGoogle Scholar
  41. 41.
    Kwok JC, Richardson DR (2003) Mol Pharmacol 63:849–861PubMedCrossRefGoogle Scholar
  42. 42.
    Kwok JC, Richardson DR (2004) Mol Pharmacol 65:181–195PubMedCrossRefGoogle Scholar
  43. 43.
    Soum E, Drapier JC (2003) J Biol Inorg Chem 8:226–232PubMedCrossRefGoogle Scholar
  44. 44.
    Lipinski P, Starzynski RR, Drapier JC, Bouton C, Bartlomiejczyk T, Sochanowicz B, Smuda E, Gajkowska A, Kruszewski M (2005) Biochem Biophys Res Commun 327:349–355PubMedCrossRefGoogle Scholar
  45. 45.
    Petrat F, de Groot H, Rauen U (2001) Biochem J 356:61–69PubMedCrossRefGoogle Scholar
  46. 46.
    Kalatzis V, Cherqui S, Antignac C, Gasnier B (2001) EMBO J 20:5940–5949PubMedCrossRefGoogle Scholar
  47. 47.
    Cherqui S, Sevin C, Hamard G, Kalatzis V, Sich M, Pequignot MO, Gogat K, Abitbol M, Broyer M, Gubler MC, Antignac C (2002) Mol Cell Biol 22:7622–7632PubMedCrossRefGoogle Scholar
  48. 48.
    Lloyd JB (1992) Biochem J 286(Pt 3):979–980PubMedGoogle Scholar
  49. 49.
    Collins DS, Unanue ER, Harding CV (1991) J Immunol 147:4054–4059PubMedGoogle Scholar
  50. 50.
    Jensen PE (1991) J Exp Med 174:1121–1130PubMedCrossRefGoogle Scholar
  51. 51.
    Watts RN, Hawkins C, Ponka P, Richardson DR (2006) Proc Natl Acad Sci USA 103:7670–7675PubMedCrossRefGoogle Scholar
  52. 52.
    Turella P, Pedersen JZ, Caccuri AM, De Maria F, Mastroberardino P, Lo BM, Federici G, Ricci G (2003) J Biol Chem 278:42294–42299PubMedCrossRefGoogle Scholar

Copyright information

© SBIC 2006

Authors and Affiliations

  • Hanna Lewandowska
    • 1
  • Sylwia Męczyńska
    • 1
  • Barbara Sochanowicz
    • 1
  • Jarosław Sadło
    • 2
  • Marcin Kruszewski
    • 1
  1. 1.Department of Radiobiology and Health ProtectionInstitute of Nuclear Chemistry and TechnologyWarsawPoland
  2. 2.Department of Radiation Chemistry and TechnologyInstitute of Nuclear Chemistry and TechnologyWarsawPoland

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