Back
 JBM  Vol.4 No.12 , December 2016
Water Efflux in Red Blood Cells of Sickle Cell Patients under Spontaneous Deoxygenation
Abstract: The water transport through Red Blood Cells (RBC) membrane has been previously studied in Sickle Cell Disease (SCD) using oxygenated RBC or under complete deoxygenation. In this work, the water efflux in RBC of sickle cell patients was studied under spontaneous deoxygenation conditions. With that purpose, a magnetic resonance method was used to evaluate the water exchange time (τe) and the permeability through the erythrocyte membrane (P) measuring the spin-spin relaxation time (T2) in doped and non-doped RBC. Carr-Purcell-Meiboon-Gill (CPMG) pulse sequence was used to measure T2 in a magnetic resonance console coupled to one homogeneous magnet system (0.095 T). An increase of the water transport in RBC from sickle cell patients was observed and characterized with a τe value of 15.2 ± 0.8 ms. The abnormal activation of the Psickle, Gardos, and potassium chloride cotransporter channels starting from deoxygenation, as well as, the possible appearance of new pores due to the increase of the hemoglobin-membrane interaction, are suggested to explain this abnormal transport phenotype. The change of the water volume to surface ratio (V/S) in the sickle cells is also suggested to be considered in P calculation under deoxygenation. The results obtained in this work increase the fundamental knowledge about molecular mechanism involved in SCD and could be useful in the development of new methods for diagnostic and treatment evaluation.
Cite this paper: Guevara, M. , Torres, Y. , Naranjo, J. , Aguilera, A. , Beyrio, L. , Felue, M. , Brada, T. and Philippé, J. (2016) Water Efflux in Red Blood Cells of Sickle Cell Patients under Spontaneous Deoxygenation. Journal of Biosciences and Medicines, 4, 152-161. doi: 10.4236/jbm.2016.412019.
References

[1]   (2014) Sickle-Cell Disease. Nature, 515, No. 7526.

[2]   Schechter, A.N., Noguchi, C.T. and Rodgers, G.P. (1987) Sickle Cell Disease. In: Stamatoyannopoulos, G., Nienhuis, A.W., Leder, P. and Majerus, P.W., Eds., The Molecular Basis of Blood Diseases, Saunders, Philadelphia, PA, 179.

[3]   Sergeant, G.R. (1997) Sickle Cell Disease. Oxford University Press, London.

[4]   Eaton, W.A. and Hofrichter, J. (1987) Hemoglobin S Gelation and Sickle Cell Disease. Blood, 70, 1245

[5]   Lores, M. and Cabal, C. (2005) Proton Magnetic Relaxation Process during the Polymerization of Hemoglobin S. Applied Magnetic Resonance, 28, 79.
https://doi.org/10.1007/BF03166995

[6]   Lores, M., Cabal, C., Nascimento, O. and Gennaro, A.M. (2006) EPR Study of the Hemoglobin Rotational Correlation Time and Microviscosity during the Polymerization of Hemoglobin S. Applied Magnetic Resonance, 30, 121-128.
https://doi.org/10.1007/BF03166986

[7]   Cabrales, Y., Lores, M. and Machado, Y. (2008) Deuterium Magnetic Relaxation Process during the Polymerization of Hemoglobin S. Applied Magnetic Resonance, 33, 207.
https://doi.org/10.1007/s00723-008-0074-z

[8]   Lores, M., Balcom, B., Cabal, C., Cabrales, Y., Falcón, J., Fernández, A., García, J.C., López, N. and Álvarez, E. (2012) Estudios de Resonancia Magnética en Anemia de Hematíes Falciformes Revista Electrónica, automática y Comunicaciones, 33, 2.

[9]   Lores, M., García, J.C., Mengana, Y. and Pereira, J. (2014) Hemoglobin S Polymerization Effect onWater Self-Diffusion Coefficient. Advances in Biological Chemistry, 4, 388-394.
https://doi.org/10.4236/abc.2014.46044

[10]   Virgilio, L., Lew, L. and Robert, M. (2005) Ion Transport Pathology in the Mechanism of Sickle Cell Dehydration. Physiological Reviews, 85, 179.
https://doi.org/10.1152/physrev.00052.2003

[11]   Hebbel, R.P. (1991) Beyond Hemoglobin Polymerization: The Red Blood Cell Membrane and Sickle Disease Pathophysiolog. Blood, 77, 214-237.

[12]   Gibson, J.S. and Ellory, J.C. (2002) Membrane Transport in Sickle Cell Disease. Blood Cells, Molecules, and Diseases, 28, 303-314.
https://doi.org/10.1006/bcmd.2002.0515

[13]   Conlon, T. and Outhred, R. (1972) Water Diffusion Permeability of Erythrocytes Using an NMR Technique. Biochimica et Biophysica Acta, 288, 354-361.
https://doi.org/10.1016/0005-2736(72)90256-8

[14]   Fabry, M.E. and Eisenstadt, M. (1975) Water Exchange between Red Cells and Plasma. Measurement by Nuclear Magnetic Relaxation. Biophysical Journal, 15, 1101-1110.
https://doi.org/10.1016/S0006-3495(75)85886-3

[15]   Morariu, V.V., Ionescu, M.S., Frangopol, M., Grosescu, R., Lupu, M. and Frangopol, P.T. (1985) Nuclear Magnetic Resonance Investigation of Human Erythrocytes in the Presence of Manganese Ions. Evidence for a Thermal Transition. Biochimica et Biophysica Acta, 815, 189-195.
https://doi.org/10.1016/0005-2736(85)90288-3

[16]   Herbst, M.D. and Goldstein, J.H. (1989) A Review of Water Diffusion Measurement by Nmr in Human Red Blood-Cells. American Journal of Physiology, 256, C1097-C1104.

[17]   Chao, L.N. and Allan Butterfield, D. (1990) The Effects of the Extracellular Manganese Concentration and Variation of the Interpulse Delay Time in the CPMG Sequence on Water Exchange Time across Erythrocyte Membranes. Biochimica et Biophysica Acta, 1028, 245-250.
https://doi.org/10.1016/0005-2736(90)90173-L

[18]   Benga, G. (2013) Comparative Studies of Water Permeability of Red Blood Cells from Humans and over 30 Animal Species: An Overview of 20 Years of Collaboration with Philip Kuchel. European Biophysics Journal, 42, 33-46.
https://doi.org/10.1007/s00249-012-0868-7

[19]   Fung, L., Narasmhan, C., Lu, H.Z. and Westerman, M.P. (1989) Reduced Water Exchange in Sickle Cell Anemia Red Cells: A Membrane Abnormality. Biochimica et Biophysica Acta, 982, 167-172.
https://doi.org/10.1016/0005-2736(89)90188-0

[20]   Craescu, C.T., Cassoly, R., Galacteros, F. and Prehu, C. (1985) Kinetics of Water Transport in Sickle Cells. Biochimica et Biophysica Acta, 812, 811-815.
https://doi.org/10.1016/0005-2736(85)90276-7

[21]   Fung, L.W., Litvin, S.D. and Reid, T.M. (1983) Spin-Label Detection of Sickle Hemoglobin-Membrane Interaction at Physiological pH. Biochemistry, 22, 864-869.
https://doi.org/10.1021/bi00273a024

[22]   Falcón-Diéguez, J.E., Rodi, P., Lores, M. and Gennaro, A.M. (2010) Spin Label Studies of the Hemoglobin-Membrane Interaction during Sickle Hemoglobin Polymerization. Applied Magnetic Resonance, 38, 443-453.
https://doi.org/10.1007/s00723-010-0138-8

[23]   Lehninger, A.L. (1981) Bioquímica: Las bases moleculares de la estructura y función celular. 2nd Edition, Editorial Pueblo y Educación, Ciudad Habana, 150.

[24]   Byun, H., Hillman, T.R., Higgins, J.M., Diez-Silva, M., Peng, Z., Dao, M., Dasari, R.R., Suresh, S. and Park, Y. (2012) Optical Measurement of Biomechanical Properties of Individual Erythrocytes from a Sickle Cell Patient. Acta Biomaterialia, 8, 4130-4138.
https://doi.org/10.1016/j.actbio.2012.07.011

[25]   Chien, S., Usami, S. and Bertles, J.F. (1970) Abnormal Rheology of Oxygenated Blood in Sickle Cell Anemia. Journal of Clinical Investigation, 49, 623-634.
https://doi.org/10.1172/JCI106273

[26]   Bertles, J.F. and Milner, P.F.A. (1968) Irreversibly Sickled Erythrocytes: A Consequence of the Heterogeneous Distribution of Hemoglobin Types in Sickle-Cell Anemia. Journal of Clinical Investigation, 47, 1731-1741.
https://doi.org/10.1172/JCI105863

[27]   Embury, S.H., Backer, K. and Glader, B.E. (1985) Mono-Valent Cation Changes in Sickle Erythrocytes—A Direct Reflection of Alpha-Globin Gene Number. Journal of Laboratory and Clinical Medicine, 106, 75-79.

[28]   Embury, S.H., Oliver, M. and Kropp, J. (2014) The Beneficial Effect of α Thalassemia on Sickle cell Anemia (SCA) Is Related to Increased Membrane Redundancy. 27th Annual Meeting. The American society of hematology.

[29]   Nash, G.B., Johnson, C.S. and Meiselman, H. (1984) Mechanical Properties of Oxygenated Red Blood Cells in Sickle Cell (HbSS) Disease. Blood, 63, 73-82.

[30]   Dong, C., Chadwick, R.S. and Schechter, A.N. (1992) Influence of Sickle Hemoglobin Polymerization and Membrane Properties on Deformability of Sickle Erythrocytes in the Microcirculation. Biophysical Journal, 63, 774-783.
https://doi.org/10.1016/S0006-3495(92)81655-7

[31]   Masys, D.R., Bromberg, P.A. and Balcerzak, S.P. (1974) Red Cells Shrink during Sickling. Blood, 44, 885-889.

[32]   Canham, P.B. and Parkinson, D.R. (1970) The Area and Volume of Single Human Erythrocytes during Gradual Osmotic Swelling to Hemolysis. Canadian Journal of Physiology and Pharmacology, 48, 369-376.
https://doi.org/10.1139/y70-059

[33]   Lew, V.L. and Bookchin, R.M. (1991) Osmotic Effects of Protein Polymerization: Analysis of Volume Changes in Sickle Cell Anemia Red Cells Following Deoxy-Hemoglobin S Polymerization. Journal of Membrane Biology, 122, 55-67.
https://doi.org/10.1007/BF01872739

[34]   Diez-Silva, M., Dao, M., Han, J., Lim, C.T. and Suresh, S. (2010) Shape and Biomechanical Characteristics of Human Red Blood Cells in Health and Disease. MRS Bulletin, 35, 382-388.
https://doi.org/10.1557/mrs2010.571

[35]   Latour, L.L., Svoboda, K., Mitra, P.P. and Sotak, C.H. (1994) Time-Dependent Diffusion of Water in a Biological Model System. Proceedings of the National Academy of Sciences of the United States of America, 91, 1229-1233.
https://doi.org/10.1073/pnas.91.4.1229

 
 
Top