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MR Relaxation Studies of Hemoglobin Aggregation Process in Sickle Cell Disease: Application for Diagnostics and Therapeutics

  • Manuel Arsenio Lores Guevara
  • Juan Carlos García Naranjo
  • Carlos Alberto Cabal Mirabal
Original Paper
  • 5 Downloads

Abstract

Sickle cell disease (SCD) is a blood disorder, which has been studied using different research methods including linear birefringence, electronic microscopy, viscosity determination, Electron Paramagnetic Resonance and Nuclear Magnetic Resonance. We summarized in this paper the contribution of proton magnetic relaxation, to the study of the behavior of the protons from protein and water as a consequence of hemoglobin S (HbS) polymerization. Spin–Lattice (T1) and Spin–Spin (T2) relaxation times have been sensitive to the agglutination of the HbS, having a decreasing behavior because of this process. T2 has shown a stronger sensitivity, decreasing immediately during deoxygenation in red blood cells (RBC) of patients homozygous for HbS and in pure HbS solution with intracellular concentration. In the HbS solutions with hemoglobin concentration below 208 mg/mL and heterozygous RBC, during induced deoxygenation, the Spin–Spin relaxation time was characterized by a delay time before polymerization, a decrease during aggregation and a further stabilization; the same occurs in the HbS solutions under spontaneous deoxygenation. The fast exchange of water molecules between the bound and free state, as well as the dipolar interaction between the protons inside the water molecules, were utilized to explain the relaxation times behavior; an increase in the correlation time of the strongly bound water was found. Contradictory results were observed between the experimental behavior obtained for T1 and those results predicted theoretically. T2 behavior showed utility to evaluate the clinical state of the SCD patients and the effect of vanillin and Hydroxyurea on the HbS polymerization.

Notes

Acknowledgements

This work has been supported by the Belgian Development Cooperation through VLIR-UOS (Flemish Interuniversity Council-University Cooperation for Development) in the context of the Institutional University Cooperation program with Universidad de Oriente. The authors also would like to thank the MRI RESEARCH CENTRE of the University of New Brunswick, Fredericton, Canada, for all the support received to finalize this work. Likewise, the authors would like to express their gratitude to Professor V.I. Chizhik for his fundamental contribution to the founding and development of our MR center and to Professor R.N. Muller for the discussion and for the opening of new possibilities in the continuation of these works.

Funding

Funder name: VLIR (Flemish University Council). Grant name: “The Universidad de Oriente promoting the sustainable development in the eastern region of Cuba”

References

  1. 1.
    L.Gravitz, S. Pincock, Nature. (2014)  https://doi.org/10.1038/515S1a
  2. 2.
    F.B. Piel, M.H. Steinberg, D.C. Rees, N. Engl. J. Med. A376, 1561 (2017)CrossRefGoogle Scholar
  3. 3.
    E.A. Ajjack, H.A. Awooda, S.E. Adalla, Int. J. Hematol. Disord. A1, 8 (2014)Google Scholar
  4. 4.
    L.V. Parise, N. Berliner, Blood A127, 789 (2016)CrossRefGoogle Scholar
  5. 5.
    M.J. Rao, K.S. Iyer, A.S. Acharya, J. Biol. Chem. A270, 19250 (1995)CrossRefGoogle Scholar
  6. 6.
    F.A. Ferrone, Experientia A49, 110 (1993)CrossRefGoogle Scholar
  7. 7.
    W.A. Eaton, H.F. Bunn, Blood A129, 2719 (2017)CrossRefGoogle Scholar
  8. 8.
    P.G. Velikov, Br. J. Haematol. A139, 173 (2007)Google Scholar
  9. 9.
    R.L. Nagel, Hemoglobin Disorders: Molecular Methods and Protocols, 1st edn. (Humana Press, Totawa, 2003), pp. 251–287CrossRefGoogle Scholar
  10. 10.
    R.L. Nagel, H. Chang, Methods Enzimol. A76, 760 (1981)CrossRefGoogle Scholar
  11. 11.
    T.R. Lindstrom, S.H. Koenig, J. Magn. Reson. A15, 344 (1974)ADSGoogle Scholar
  12. 12.
    G.L. Cottam, K.M. Valentine, K. Yamaoka, M.R. Waterman, Arch. Biochem. Biophys. A162, 487 (1974)CrossRefGoogle Scholar
  13. 13.
    B.C. Thompson, M.R. Waterman, G.L. Cottam, Arch. Biochem. Biophys. A166, 193 (1975)CrossRefGoogle Scholar
  14. 14.
    G.L. Cottam, M.R. Waterman, Arch. Biochem. Biophys. A177, 293 (1976)CrossRefGoogle Scholar
  15. 15.
    M.R. Waterman, G.L. Cottam, Biochem. Biophys. Res. Commun. A73, 639 (1976)CrossRefGoogle Scholar
  16. 16.
    K. Shibata, M.R. Waterman, G.L. Cottam, J. Biol. Chem. A252, 7468 (1977)Google Scholar
  17. 17.
    G.L. Cottam, M.R. Waterman, B.C. Thompson, Arch. Biochem. Biophys. A181, 61 (1977)CrossRefGoogle Scholar
  18. 18.
    A. Zipp, I.D. Kuntz, S.J. Rehfeld, S.B. Shohet, FEBS Lett. A43, 9 (1974)CrossRefGoogle Scholar
  19. 19.
    A. Zipp, T.L. James, I.D. Kuntz, S.B. Shohet, Biochim. Biophys. Acta A 428, 291 (1976)CrossRefGoogle Scholar
  20. 20.
    W.A. Eaton, J. Hofrichter, P.D. Ross, R.G. Tschudin, E.D. Becker, Biochem. Biophys. Res. Commun. A69, 538 (1976)CrossRefGoogle Scholar
  21. 21.
    H. Chuang, M.R. Waterman, K. Yamaoka, G.L. Cottam, Arch. Biochem. Biophys. A167, 145 (1975)CrossRefGoogle Scholar
  22. 22.
    J. Losada, F. Gilart, C. Cabal, H.Fleitas, L. Valiente, J. Robier, Proceedings of the 24th Ampere Congress, Magnetic Resonance and Related Phenomena (Poznan, 1988) p. 1027Google Scholar
  23. 23.
    K.R. bridges, G.D. Barabino, C. Brugnara, M.R. Cho, G.W. Christoph, G. Dover, B.M. Ewestein, D.E. Golan, C.R.G. Guttmann, J. Hofrichter, R.V. MUlkern, B. Zhang, W.E. Eaton, Blood A88, 4701 (1996)Google Scholar
  24. 24.
    I.M. Russu, C. Ho, Proc. Natl. Acad. Sci. USA A77, 6577 (1980)ADSCrossRefGoogle Scholar
  25. 25.
    M. Lores, C. Cabal, Appl. Magn. Reson. A 28, 79 (2005)CrossRefGoogle Scholar
  26. 26.
    M. Lores, PhD Thesis, Universidad de Oriente, Santiago de Cuba, Cuba (2005)Google Scholar
  27. 27.
    T.L. James, R. Matthews, G.B. Matson, Biopolymers A18, 1763 (1979)CrossRefGoogle Scholar
  28. 28.
    M. Lores, C. Cabal, O. Nascimento, A.M. Gennaro, Appl. Magn. Reson. A30, 121 (2006)CrossRefGoogle Scholar
  29. 29.
    Y. Cabrales, M. Lores, Y. Machado, Appl. Magn. Reson. A33, 207 (2008)CrossRefGoogle Scholar
  30. 30.
    M.A. Lores-Guevara, Y. Mengana-Torres, J. García-Naranjo, A. Ramírez-Aguilera, L.C. Suárez-Beyrio, M.A. Marichal-Felue, T. Simón-Brada, J. Philippé, J. Biosci. Med. A4, 152 (2016)Google Scholar
  31. 31.
    M.A. Lores-Guevara, J. García-Naranjo, Y. Mengana-Torres, Adv. Biol. Chem. A4, 388 (2014)CrossRefGoogle Scholar
  32. 32.
    A. Fernández, C. Cabal, M. Lores, J. Losada, E. Pérez, Hemoglobin A33, 206 (2009)CrossRefGoogle Scholar
  33. 33.
    G. Del Toro-García, J.E. Falcón-Dieguez, Y. Alonso-Geli, Y.C. Valdés-Rodríguez, C.A. Cabal Mirabal, Bioquimia A28, 4 (2003)Google Scholar
  34. 34.
    A. Fernández, C. Cabal, J. Losada, E. Álvarez, C. Soler, J. Otero, Hemoglobin A29, 181 (2005)Google Scholar

Copyright information

© Springer-Verlag GmbH Austria, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Centro de Biofísica MédicaUniversidad de OrienteSantiago de CubaCuba
  2. 2.Facultad de FísicaUniversidad de la HabanaHabanaCuba

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