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Comparison of interaction between ceruloplasmin and lactoferrin/transferrin: to bind or not to bind

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Abstract

The year 2016 marked the 50th anniversary of the discovery by S. Osaki who first showed that ceruloplasmin (CP, ferro:O2-oxidoreductase or ferroxidase) is capable of oxidizing Fe(II) to Fe(III) and favors the incorporation of the latter into transferrin (TF). However, much debate remains in the literature concerning the existence of a complex between the enzyme oxidizing iron and the protein facilitating its transport in plasma. We studied CP in exocrine fluids and demonstrated its high-affinity interaction with transferrin found in breast milk and in lacrimal fluid, i.e. with lactoferrin (LF). Here we present data obtained by comparing the interaction of CP with LF and TF using surface plasmon resonance and Hummel–Dreyer chromatography. Binding of apo-LF within the range of concentrations 1.6-51.3 μM with CP immobilized on a CM5-chip is characterized by K D = 1.07 μM. Under similar conditions, the K D for apo-TF was measured and appeared to be higher than 51.3 μM. Hummel–Dreyer chromatography of CP with 51 μM apo-LF/apo-TF in the effluent demonstrated the absence of interaction between apo-TF and CP in solution, contrary to efficient interaction between apoLF and CP. In contrast to LF, the interaction of apo-TF with CP is probably not stable within the physiological range of concentrations of TF.

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Abbreviations

A:

analyte

CP:

ceruloplasmin

k a :

association rate constant

k d :

dissociation rate constant

K D :

equilibrium dissociation constant

LF:

lactoferrin

Rmax :

analyte binding capacity of surface

RU:

resonance units

SPR:

surface plasmon resonance

TF:

transferrin

References

  1. Vashchenko, G., and MacGillivray, R. T. (2013) Multicopper oxidases and human iron metabolism, Nutrients, 5, 2289–2313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Osaki, S. (1966) Kinetic studies of ferrous ion oxidation with crystalline human ferroxidase (ceruloplasmin), J. Biol. Chem., 241, 5053–5059.

    CAS  PubMed  Google Scholar 

  3. Sokolov, A. V., Zakharova, E. T., Shavlovskii, M. M., and Vasil’ev, V. B. (2005) Isolation of stable human ceruloplasmin and its interaction with salmon protamine, Bioorg. Khim., 31, 269–279.

    CAS  PubMed  Google Scholar 

  4. Sokolov, A. V., Kostevich, V. A., Romanico, D. N., Zakharova, E. T., and Vasilyev, V. B. (2012) Two-stage method for purification of ceruloplasmin based on its interaction with neomycin, Biochemistry (Moscow), 77, 631–638.

    Article  CAS  Google Scholar 

  5. Hudson, D. M., Krisinger, M. J., Griffiths, T. A., and Macgillivray, R. T. (2008) Neither human hephaestin nor ceruloplasmin forms a stable complex with transferrin, J. Cell. Biochem., 103, 1849–1855.

    Article  CAS  PubMed  Google Scholar 

  6. Zakharova, E. T., Shavlovski, M. M., Bass, M. G., Gridasova, A. A., Pulina, M. O., De Filippis, V., Beltramini, M., Di Muro, P., Salvato, B., Fontana, A., Vasilyev, V. B., and Gaitskhoki, V. S. (2000) Interaction of lactoferrin with ceruloplasmin, Arch. Biochem. Biophys., 374, 222–228.

    Article  CAS  PubMed  Google Scholar 

  7. Sokolov, A. V., Pulina, M. O., Zakharova, E. T., Susorova, A. S., Runova, O. L., Kolodkin, N. I., and Vasilyev, V. B. (2006) Identification and isolation from breast milk of ceruloplasmin–lactoferrin complex, Biochemistry (Moscow), 71, 160–166.

    Article  CAS  Google Scholar 

  8. Sokolov, A. V., Pulina, M. O., Runova, O. L., Zakharova, E. T., and Vasilyev, V. B. (2013) Complex of ceruloplasmin and lactoferrin in tear fluid, Med. Acad. J., 13, 39–43.

    Google Scholar 

  9. Ha-Duong, N. T., Eid, C., Hemadi, M., and El Hage Chahine, J. M. (2010) In vitro interaction between ceruloplasmin and human serum transferrin, Biochemistry, 49, 10261–10263.

    Article  CAS  PubMed  Google Scholar 

  10. Eid, C., Hemadi, M., Ha-Duong, N. T., and El Hage Chahine, J. M. (2014) Iron uptake and transfer from ceruloplasmin to transferrin, Biochim. Biophys. Acta, 1840, 1771–1781.

    Article  CAS  PubMed  Google Scholar 

  11. Sokolov, A. V., Pulina, M. O., Zakharova, E. T., Shavlovski, M. M., and Vasilyev, V. B. (2005) Effect of lactoferrin on the ferroxidase activity of ceruloplasmin, Biochemistry (Moscow), 70, 1015–1019.

    Article  CAS  Google Scholar 

  12. Sokolov, A. V., Ageeva, K. V., Pulina, M. O., Zakharova, E. T., and Vasilyev, V. B. (2009) Effect of lactoferrin on oxidative features of ceruloplasmin, Biometals, 22, 521–529.

    Article  CAS  PubMed  Google Scholar 

  13. Sabatucci, A., Vachette, P., Vasilyev, V. B., Beltramini, M., Sokolov, A., Pulina, M., Salvato, B., Angelucci, C. B., Maccarrone, M., Cozzani, I., and Dainese, E. (2007) Structural characterization of the ceruloplasmin–lactoferrin complex in solution, J. Mol. Biol., 371, 1038–1046.

    Article  CAS  PubMed  Google Scholar 

  14. White, K. N., Conesa, C., Sanchez, L., Amini, M., Farnaud, S., Lorvoralak, C., and Evans, R. W. (2012) The transfer of iron between ceruloplasmin and transferrins, Biochim. Biophys. Acta, 1820, 411–416.

    Article  CAS  PubMed  Google Scholar 

  15. Sokolov, A. V., Prozorovski, V. N., and Vasilyev, V. B. (2009) Biochemistry (Moscow), 74, 1225–1227.

    Article  CAS  Google Scholar 

  16. Samygina, V. R., Sokolov, A. V., Bourenkov, G., Petoukhov, M. V., Pulina, M. O., Zakharova, E. T., Vasilyev, V. B., Bartunik, H., and Svergun, D. I. (2013) Ceruloplasmin: macromolecular assemblies with iron-containing acute phase proteins, PLoS One, 8, e67145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sokolov, A. V., Zakharova, E. T., Kostevich, V. A., Samygina, V. R., and Vasilyev, V. B. (2014) Lactoferrin, myeloperoxidase, and ceruloplasmin: complementary gearwheels cranking physiological and pathological processes, Biometals, 27, 815–828.

    Article  CAS  PubMed  Google Scholar 

  18. Pulina, M. O., Zakharova, E. T., Sokolov, A. V., Shavlovski, M. M., Bass, M. G., Solovyov, K. V., Kokryakov, V. N., and Vasilyev, V. B. (2002) Studies of the ceruloplasmin–lactoferrin complex, Biochem. Cell Biol., 80, 35–39.

    Article  CAS  PubMed  Google Scholar 

  19. Sokolov, A. V., Acquasaliente, L., Kostevich, V. A., Frasson, R., Zakharova, E. T., Pontarollo, G., Vasilyev, V. B., and De Filippis, V. (2015) Thrombin inhibits the antimyeloperoxidase and ferroxidase functions of ceruloplasmin: relevance in rheumatoid arthritis, Free Radic. Biol. Med., 86, 279–294.

    Article  CAS  PubMed  Google Scholar 

  20. Kostevich, V. A., Sokolov, A. V., Grudinina, N. A., Zakharova, E. T., Samygina, V. R., and Vasilyev, V. B. (2015) Interaction of macrophage migration inhibitory factor with ceruloplasmin: role of labile copper ions, Biometals, 28, 817–826.

    Article  CAS  PubMed  Google Scholar 

  21. Noyer, M., Dwulet, F. E., Hao, Y. L., and Putman, F. V. (1980) Purification and characterization of undegraded human ceruloplasmin, Anal. Biochem., 102, 450–458.

    Article  CAS  PubMed  Google Scholar 

  22. Masson, P. L. (1970) in La Lactoferrine. Proteine des Secretions Externes et des Leucocytes Neutrophiles (Arscia, S. A., ed.) Brussels.

  23. Davis, B. J. (1964) Disc electrophoresis. II. Method and application to human serum proteins, Ann. N. Y. Acad. Sci., 121, 404–427.

    Article  CAS  PubMed  Google Scholar 

  24. Sokolov, A. V., Pulina, M. O., Ageeva, K. V., Ayrapetov, M. I., Berlov, M. N., Volgin, G. N., Markov, A. G., Yablonsky, P. K., Kolodkin, N. I., Zakharova, E. T., and Vasilyev, V. B. (2007) Interaction of ceruloplasmin, lactoferrin, and myeloperoxidase, Biochemistry (Moscow), 72, 409–415.

    Article  CAS  Google Scholar 

  25. Pulina, M. O., Sokolov, A. V., Zakharova, E. T., Kostevich, V. A., and Vasilyev, V. B. (2010) Effect of lactoferrin on consequences of acute experimental hemorrhagic anemia in rats, Bull. Exp. Biol. Med., 149, 219–222.

    Article  CAS  PubMed  Google Scholar 

  26. Zakharova, E. T., Kostevich, V. A., Sokolov, A. V., and Vasilyev, V. B. (2012) Human apo-lactoferrin as a physiological mimetic of hypoxia stabilizes hypoxia-inducible factor-1 alpha, Biometals, 25, 1247–1259.

    Article  CAS  PubMed  Google Scholar 

  27. Kostevich, V. A., Sokolov, A. V., Kozlov, S. O., Vlasenko, A. Y., Kolmakov, N. N., Zakharova, E. T., and Vasilyev, V. B. (2016) Functional link between ferroxidase activity of ceruloplasmin and protective effect of apo-lactoferrin: studying rats kept on a silver chloride diet, Biometals, 29, 691–704.

    Article  CAS  PubMed  Google Scholar 

  28. Sokolov, A. V., Solovyov, K. V., Kostevich, V. A., Chekanov, A. V., Pulina, M. O., Zakharova, E. T., Shavlovski, M. M., Panasenko, O. M., and Vasilyev, V. B. (2012) Protection of ceruloplasmin by lactoferrin against hydroxyl radicals is pH-dependent, Biochem. Cell Biol., 90, 397–404.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Experimental Medicine, 197376, St. Petersburg, Russia

    A. V. Sokolov, I. V. Voynova, V. A. Kostevich, A. Yu. Vlasenko, E. T. Zakharova & V. B. Vasilyev

  2. St. Petersburg State University, 199000, St. Petersburg, Russia

    A. V. Sokolov & V. B. Vasilyev

Authors
  1. A. V. Sokolov
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  2. I. V. Voynova
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  3. V. A. Kostevich
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  4. A. Yu. Vlasenko
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  5. E. T. Zakharova
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  6. V. B. Vasilyev
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Corresponding author

Correspondence to A. V. Sokolov.

Additional information

Published in Russian in Biokhimiya, 2017, Vol. 82, No. 9, pp. 1374-1380.

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Sokolov, A.V., Voynova, I.V., Kostevich, V.A. et al. Comparison of interaction between ceruloplasmin and lactoferrin/transferrin: to bind or not to bind. Biochemistry Moscow 82, 1073–1078 (2017). https://doi.org/10.1134/S0006297917090115

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  • DOI: https://doi.org/10.1134/S0006297917090115

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