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.
Similar content being viewed by others
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
Drapier JC, Pellat C, Henry Y (1991) J Biol Chem 266:10162–10167
Bastian NR, Yim CY, Hibbs JB Jr, Samlowski WE (1994) J Biol Chem 269:5127–5131
Pieper GM, Halligan NL, Hilton G, Konorev EA, Felix CC, Roza AM, Adams MB, Griffith OW (2003) Proc Natl Acad Sci USA 100:3125–3130
Pillay CS, Elliott E, Dennison C (2002) Biochem J 363:417–429
Vanin AF, Malenkova IV, Serezhenkov VA (1997) Nitric Oxide 1:191–203
Costanzo S, Menage S, Purrello R, Bonomo RP, Fontecave M (2001) Inorg Chim Acta 318:1–7
Vanin A, Kleschyov A (1999) In: Lukiewicz S, Zweier JL (eds) Nitric oxide in transplant rejection and anti-tumor defence. Kluwer, Boston, pp 49–82
Ueno T, Yoshimura T (2000) Jpn J Pharmacol 82:95–101
Vanin AF (1998) Biochemistry (Moscow) 63:782–793
Keese MA, Bose M, Mulsch A, Schirmer RH, Becker K (1997) Biochem Pharmacol 54:1307–1313
Henry Y, Ducrocq C, Drapier JC, Servent D, Pellat C, Guissani A (1991) Eur Biophys J 20:1–15
Kim YM, Chung HT, Simmons RL, Billiar TR (2000) J Biol Chem 275:10954–10961
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 280:42172–42180
Kruszewski M (2003) Mutation Res 531:81–92
Kurz T, Gustafsson B, Brunk UT (2006) FEBS J 273:3106–3117
Kroemer G, Jaattela M (2005) Nat Rev Cancer 5:886–897
Klionsky DJ, Emr SD (2000) Science 290:1717–1721
Cuervo AM, Dice JF (1998) J Mol Med 76:6–12
Roberts S, Bomford A (1988) J Biol Chem 263:19181–19187
Radisky DC, Kaplan J (1998) Biochem J 336(Pt 1):201–205
Persson HL, Nilsson KJ, Brunk UT (2001) Redox Rep 6:57–63
Yu Z, Persson HL, Eaton JW, Brunk UT (2003) Free Radic Biol Med 34:1243–1252
Tenopoulou M, Doulias PT, Barbouti A, Brunk U, Galaris D (2005) Biochem J 387:703–710
Persson HL, Kurz T, Eaton JW, Brunk UT (2005) Biochem J 389:877–884
Zanninelli G, Glickstein H, Breuer W, Milgram P, Brissot P, Hider RC, Konijn AM, Libman J, Shanzer A, Cabantchik ZI (1997) Mol Pharmacol 51:842–852
Laub R, Schneider YJ, Octave JN, Trouet A, Crichton RR (1985) Biochem Pharmacol 34:1175–1183
Cable H, Lloyd JB (1999) J Pharm Pharmacol 51:131–134
Graham JM (1993) Methods Mol Biol 19:29–40
Kennedy MC, Antholine WE, Beinert H (1997) J Biol Chem 272:20340–20347
Kurz T, Leake A, von Zglinicki T, Brunk UT (2004) Biochem J 378:1039–1045
de Duve C, de Barsy T, Poole B, Trouet A, Tulkens P, van Hoof F (1974) Biochem Pharmacol 23:2495–2531
Ignarro LJ (ed.) (2000) Nitric oxide: biology and pathobiology. Academic, San Diego
Quintana C, Bellefqih S, Laval JY, Guerquin-Kern JL, Wu TD, Avila J, Ferrer I, Arranz R, Patino C (2006) J Struct Biol 153:42–54
Bienfait HF, van den Briel ML (1980) Biochim Biophys Acta 631:507–510
Funk F, Lenders JP, Crichton RR, Schneider W (1985) Eur J Biochem 152:167–172
Bolann BJ, Ulvik RJ (1987) Biochem J 243:55–59
Hernandez-Yago J, Knecht E, Martinez-Ramon A, Grisolia S (1980) Cell Tissue Res 205:303–309
Konijn AM, Glickstein H, Vaisman B, Meyron-Holtz EG, Slotki IN, Cabantchik ZI (1999) Blood 94:2128–2134
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–F1533
Gruper Y, Bar J, Bacharach E, Ehrlich R (2005) J Cell Physiol 204:901–912
Kwok JC, Richardson DR (2003) Mol Pharmacol 63:849–861
Kwok JC, Richardson DR (2004) Mol Pharmacol 65:181–195
Soum E, Drapier JC (2003) J Biol Inorg Chem 8:226–232
Lipinski P, Starzynski RR, Drapier JC, Bouton C, Bartlomiejczyk T, Sochanowicz B, Smuda E, Gajkowska A, Kruszewski M (2005) Biochem Biophys Res Commun 327:349–355
Petrat F, de Groot H, Rauen U (2001) Biochem J 356:61–69
Kalatzis V, Cherqui S, Antignac C, Gasnier B (2001) EMBO J 20:5940–5949
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 22:7622–7632
Lloyd JB (1992) Biochem J 286(Pt 3):979–980
Collins DS, Unanue ER, Harding CV (1991) J Immunol 147:4054–4059
Jensen PE (1991) J Exp Med 174:1121–1130
Watts RN, Hawkins C, Ponka P, Richardson DR (2006) Proc Natl Acad Sci USA 103:7670–7675
Turella P, Pedersen JZ, Caccuri AM, De Maria F, Mastroberardino P, Lo BM, Federici G, Ricci G (2003) J Biol Chem 278:42294–42299
Acknowledgement
This work was supported by a statutory grant for INTC.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lewandowska, H., Męczyńska, S., Sochanowicz, B. et al. Crucial role of lysosomal iron in the formation of dinitrosyl iron complexes in vivo. J Biol Inorg Chem 12, 345–352 (2007). https://doi.org/10.1007/s00775-006-0192-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00775-006-0192-8