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

Authors

  • Hanna Lewandowska
    • Department of Radiobiology and Health ProtectionInstitute of Nuclear Chemistry and Technology
  • Sylwia Męczyńska
    • Department of Radiobiology and Health ProtectionInstitute of Nuclear Chemistry and Technology
  • Barbara Sochanowicz
    • Department of Radiobiology and Health ProtectionInstitute of Nuclear Chemistry and Technology
  • Jarosław Sadło
    • Department of Radiation Chemistry and TechnologyInstitute of Nuclear Chemistry and Technology
    • Department of Radiobiology and Health ProtectionInstitute of Nuclear Chemistry and Technology
Original Paper

DOI: 10.1007/s00775-006-0192-8

Cite this article as:
Lewandowska, H., Męczyńska, S., Sochanowicz, B. et al. J Biol Inorg Chem (2007) 12: 345. doi:10.1007/s00775-006-0192-8

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 cellsElectron paramagnetic resonanceNitric oxideSalicylaldehyde isonicotinoyl hydrazoneDesferrioxamine 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

Copyright information

© SBIC 2006