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Conformational Changes and Oxidation of Membrane Proteins in Senescent Human Erythrocytes

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 307))

Abstract

Human red cells spend 120 days in the circulation and are then removed in an age-dependent manner (1). Since cell destruction is age-dependent, studies about red cell senescence focused on the mechanisms by which the aging of the cell leads to its destruction. The presence of autoantibodies on the surface of senescent cells produced the development of the autoimmune hypothesis for senescent cell removal from the circulation (2–4), and raised questions about the presence of senescence markers on the cell surface that permit such recognition and the mechanisms of their development during red cell life span. Studies on surface changes taking place during red cell senescence have been carried out mainly on density-separated red cells (5). A reduction in membrane surface area in the dense cell population is evident as a decrease in membrane cholesterol and phospholipid content (6,7) and in acetylcholinesterase activity and sialic acid content (8). Cell deformability decreases (9–12) and at the level of the membrane slight modifications of the covalent structure of some components have been described, produced by processes like oxidation (13–15), proteolysis (16, 17), glycation (18), methylation and transamidation (19), phosphorylation (20), and modifications of phospholipid asimmetry (21) and of topology and topography of proteins have been reported or hypothesized (22–25). Most of these modifications are effective in promoting autoantibody binding and/or phagocytosis in vitro, thus supporting a possible role of these mechanisms in determining recognition and removal of senescent cells. Investigations carried out with in vivo (26,27) and in vitro models (28,29) for red cell senescence and studies with mutant erythrocytes showed that oxidation plays a relevant role in determining surface properties of senescent cells and of many pathological cells with a decreased life span (30–32). Since the oxidative state of membrane proteins in human red cells of different age has not been investigated in detail in the past, we tried to quantitate the oxidative lesion the membrane proteins undergo during red cell life-span, in an attempt to understand what kind of membrane processes expressed in senescent red cells can be related to oxidation.

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References

  1. G. S. Eadie and I. W. Brown, Red blood cell survival studies, Blood 8:1110 (1953).

    PubMed  CAS  Google Scholar 

  2. M. M. B. Kay, Mechanism of removal of senescent cells by human macrophages “in situ”, Proc. Natl. Acad. Sci. USA 72:3521 (1975).

    Article  PubMed  CAS  Google Scholar 

  3. M. M. B. Kay, Role of physiologic autoantibody in the removal of senescent human red cells, J. Supramol. Struct. 9:555 (1978).

    Article  PubMed  CAS  Google Scholar 

  4. H. U. Lutz and G. Stringaro-Wipf, Senescent red cell-bound IgG is attached to band 3 protein, Biomed. Biochim. Acta 42:S117 (1983).

    PubMed  CAS  Google Scholar 

  5. M. R. Clark, Senescence of red blood cells: progress and problems, Physiol. Rev. 68:503 (1988).

    PubMed  CAS  Google Scholar 

  6. M. P. Westerman, L. E. Pierce and W. N. Jensen, Erythrocyte lipids: a comparison of normal young and normal old populations, J. Lab. Clin. Med. 62:394 (1963).

    PubMed  CAS  Google Scholar 

  7. C. C. Winterbourn and R. D. Batt, Lipid composition of human red cells of different ages, Biochim. Biophys. Acta 202:1 (1970).

    PubMed  CAS  Google Scholar 

  8. N. S. Cohen, J. E. Ekholm, M. G. Luthra and D. J. Hanahan, Biochemical characterization of density-separated human erythrocytes, Biochim. Biophys. Acta 419:229 (1976).

    Article  PubMed  CAS  Google Scholar 

  9. M. R. Clark, N. Mohandas and S. B. Shohet, Osmotic gradient ektacytometry: comprehensive characterization of red cell volume and surface maintenance, Blood 61:899 (1983).

    PubMed  CAS  Google Scholar 

  10. G. B. Nash and H. J. Meiselman, Red Cell and ghost viscoelasticity. Effects of hemoglobin concentration and in vivo aging, Biophys. J. 43:63 (1983).

    Article  PubMed  CAS  Google Scholar 

  11. R I. Weed, The importance of erythrocyte deformability, Am. J. Med. 49:147 (1970).

    Article  PubMed  CAS  Google Scholar 

  12. A. R. Williams and D.R. Morris, The internal viscosity of the human erythrocyte may determine its life-span in vivo, Scand. J. Haematol. 24:57 (1980).

    Article  PubMed  CAS  Google Scholar 

  13. L. M. Snyder, L. Leb, J. Piotrowski, N. Sauberman, S. C. Liu and N. L. Fortier, Irreversible spectrin-haemoglobin crosslinking in vivo: a marker for red cell senescence, Brit. J. Haematol. 53:379 (1983).

    Article  CAS  Google Scholar 

  14. H. Q. Campwala and J. F. Desforges, Membrane-bound hemichrome in density-separated cohorts of normal (AA) and sickled (SS) cells, J. Lab. Clin. Med. 99:25 (1982).

    PubMed  CAS  Google Scholar 

  15. S. K. Jain, Evidence for membrane lipid peroxidation during the in vivo aging of human erythrocytes, Biochim. Biophys. Acta 937:205 (1988).

    Article  PubMed  CAS  Google Scholar 

  16. M. Morrison, K. S. Au and L. Hsu, Are the red cell proteases a clock mechanism which turns on a signal of senescence?, Biomed. Biochim. Acta 46:S79 (1987).

    PubMed  CAS  Google Scholar 

  17. M. M. B. Kay and J. R. Goodman, IgG antibodies do not bind to band 3 in intact erythrocytes; enzymatic treatment of cells is required for IgG binding, Biomed. Biochim. Acta 43:841 (1984).

    PubMed  CAS  Google Scholar 

  18. S. P. Sutera, R. A. Gardner, C. W. Boylan, G. L. Carrol, K. C. Chang, J. S. Marvel, C. Kilo, B. Gonen and J. R. Williamson, Age-related changes in deformability of human erythrocytes, Blood 65:275 (1985).

    PubMed  CAS  Google Scholar 

  19. J. R. Barber and S. Clarke, Membrane protein carboxyl methylation increases with human erythrocyte age, J. Biol. Chem. 258:1189 (1983).

    PubMed  CAS  Google Scholar 

  20. G. Fairbanks, J. Palek, J. E. Dino and P. A. Liu, Protein kinase and membrane protein phosphorylation in normal and abnormal human erythrocytes: variation related to mean cell age, Blood 61:850 (1983).

    PubMed  CAS  Google Scholar 

  21. R. A. Schlegel, L. McEvoy, M. Weiser and P. Williamson, Phospholipid organization as a determinant of red cell recognition by the reticuloendothelial system, in: “Red blood cells as carriers for drugs-Potential therapeutic applications”, C. Ropars, M. Chassaigne and C. Nicolau eds., Vol. 67, Pergamon Press, Oxford (1987).

    Google Scholar 

  22. E. Schweizer, W. Angst and H. U. Lutz, Glycoprotein topology on intact human red blood cells reevaluated by cross-linking following amino group supplementation, Biochemistry 21:6807 (1982).

    Article  PubMed  CAS  Google Scholar 

  23. H. U. Lutz, R. Flepp and G. Stringaro-Wipf, Naturally occurring autoantibodies to exoplasmic and cryptic regions of band 3 protein, the major integral membrane protein of human red blood cells, J. Immunol. 133:2610 (1984).

    PubMed  CAS  Google Scholar 

  24. P. S. Low, S. M. Waugh, K. Zinke and D. Drenckhahn, The role of hemoglobin denaturation and band 3 clustering in red blood cell aging, Science 227:531 (1985).

    Article  PubMed  CAS  Google Scholar 

  25. M. M. B. Kay, G. J. C. G. M. Bosman and C. Lawrence, Functional topography of band 3: specific structural alteration linked to functional aberrations in human erythrocytes, Proc. Natl. Acad. Sci. U.S.A. 85:492 (1988).

    Article  PubMed  CAS  Google Scholar 

  26. G. J. Johnson, D. W. Allen, T. P. Flynn, B. Finkel and J. G. White, Decreased survival ‘in vivo’ of diamide-incubated dog erythrocytes, J. Clin. Invest. 66:955 (1980).

    Article  PubMed  CAS  Google Scholar 

  27. M. M.B. Kay, G. J. C. G. M. Bosman, S. S. Shapiro, A. Bendich and P. S. Bassel, Oxidation as a possible mechanism of cellular aging: vitamin E deficiency causes premature aging and IgG binding to erythrocytes. Proc. Natl. Acad. Sci.USA 83:2463 (1986).

    Article  PubMed  CAS  Google Scholar 

  28. P. Arese, F. Bussolino, R. Flep, P. Stammler, S. Fasler and H. U. Lutz, Diamide enhances phagocytosis of human red cell in a complement and anti band 3 antibody-dependent process, Biomed. Biochim. Acta 46:S84 (1987).

    PubMed  CAS  Google Scholar 

  29. M. Beppu, A. Mizukami, M. Nagoya and K. Kikugawa, Binding of anti-band 3 autoantibody to oxidatively damaged erythrocytes, J. Biol. Chem. 265:3226 (1990).

    PubMed  CAS  Google Scholar 

  30. B. H. Rank, J. Carlsson and R.P. Hebbel, Abnormal redox status of membrane-protein thiols in sickle erythrocytes, J. Clin. Invest. 75:1531 (1985).

    Article  PubMed  CAS  Google Scholar 

  31. P. S. Becker, J. S. Morrow and S. E. Lux, Abnormal oxidant sensitivity and-chain structure of spectrin in hereditary spherocytosis associated with defective spectrin-4.1 binding, J. Clin. Invest. 80:557 (1987).

    Article  PubMed  CAS  Google Scholar 

  32. P. Arese and A. De Flora, Pathophysiology of hemolysis in glucose-6-phosphate dehydrogenase deficiency, Semin. Hematol. 27:1 (1990).

    PubMed  CAS  Google Scholar 

  33. N. S. Kosower, E. M. Kosower and B. Wertheim, Diamide, a new reagent for the intracellular oxidation of glutathione to the disulfide, Biochem. Biophys. Res. Commun. 37:593 (1969).

    Article  PubMed  CAS  Google Scholar 

  34. E. Beutler, C. West and K. G. Blume, The removal of leukocytes and plateles from whole blood, J. Lab. Clin. Med. 88:328 (1976).

    PubMed  CAS  Google Scholar 

  35. A. Brovelli, C. Seppi, G. Pallavicini and C. Balduini, Membrane processes during ‘in vivo’ aging of human erythrocytes, Biomed. Biochim. Acta 42:S122 (1983).

    PubMed  CAS  Google Scholar 

  36. J. R. Murphy, Influence of temperature and method of centrifugation on the separation of erythrocytes, J. Lab. Clin. Med. 82:334 (1973).

    PubMed  CAS  Google Scholar 

  37. W. J. Griffiths, The determination of creatine in body fluid and muscle and of phosphocreatine in muscle, using the autoanalyzer, Clin. Chim. Acta 9:210 (1964).

    Article  PubMed  CAS  Google Scholar 

  38. J. Fehr and M. Knob, Comparison of red cell creatine level and reticulocyte count in appraising the severity of hemolytic processes, Blood 53:966 (1979).

    PubMed  CAS  Google Scholar 

  39. V.T. Marchesi and J. E. Palade, The localization of Mg-Na-K-activated adenosine triphosphatase on red cell ghost membranes, J. Cell Biol. 35:385 (1967).

    Article  PubMed  CAS  Google Scholar 

  40. K. Yamamoto, T. Sekine and Y. Kanaoka, Fluorescent thiol reagents-Fluorescent tracer method for protein SH groups using N-(7-dimethylamino-4-methyl-coumarinyl) maleimide. An application to the proteins separated by SDS-polyacrylamide gel electrophoresis, Anal. Biochem. 79:83 (1977).

    Article  PubMed  CAS  Google Scholar 

  41. A. Brovelli, C. Seppi, A. M. Castellana, M. R. De Renzis, A. Blasina and C. Balduini, Oxidative lesion to membrane proteins in senescent erythrocytes, Biomed. Biochim. Acta 49:S218 (1990).

    PubMed  CAS  Google Scholar 

  42. E. Nigg, M. Kessler and R. J. Cherry, Labeling of human erythrocyte membranes with eosin probes used for protein diffusion measurements-Inhibition of anion transport and photooxidative inactivation of acetylcholinesterase, Biochim. Biophys. Acta 550:328 (1979).

    Article  PubMed  CAS  Google Scholar 

  43. T. Chiba, Y. Sato and Y. Suzuki, Characterization of eosin 5-isothiocyanate binding site in band 3 protein of the human erythrocyte, Biochim. Biophys. Acta 897:14 (1987).

    Article  PubMed  CAS  Google Scholar 

  44. M. K. Ho and G. Guidotti, A membrane protein from human erythrocytes involved in anion exchange, J. Biol. Chem. 250:675 (1975).

    PubMed  CAS  Google Scholar 

  45. C. Seppi, M. A. Castellana, G. Minetti, G. Piccinini, C. Balduini and A. Brovelli, Evidence for membrane protein oxidation during ‘in vivo’ aging of human erythrocytes, Mech. Age. Dev. in press.

    Google Scholar 

  46. U. K. Laemmli, Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature 227:680 (1970).

    Article  PubMed  CAS  Google Scholar 

  47. O. H. Lowry, N. J. Rosebrough, A. L. Farr and R. J. Randall, Protein measurement with the Folin phenol reagent, J. Biol. Chem. 193:265 (1951).

    PubMed  CAS  Google Scholar 

  48. E. Beutler, The preparation of red cells for assay, in “Red cell metabolism — A manual of Biochemical methods” 3rd edition, Grune and Stratton, New York (1984).

    Google Scholar 

  49. D. Jay and L. Cantley, Structural aspects of the red cell anion exchange protein, Ann. Rev. Biochem. 55:511 (1986).

    Article  PubMed  CAS  Google Scholar 

  50. R. L. Levine, C. N. Oliver, R. M. Fulks and E. R. Stadtman, Turnover of bacterial glutamine synthetase: oxidative inactivation precedes proteolysis, Proc. Natl. Acad. Sci. USA 78:2120 (1981).

    Article  PubMed  CAS  Google Scholar 

  51. A. J. Rivett, Preferential degradation of the oxidatively modified form of glutamine synthetase by intracellular mammalian proteases, J. Biol. Chem. 260:300 (1985).

    PubMed  CAS  Google Scholar 

  52. K. J. A. Davies and A. L. Goldberg, Proteins damaged by oxygen radicals are rapidly degraded in extracts of red blood cells, J. Biol. Chem. 262:8227 (1987).

    PubMed  CAS  Google Scholar 

  53. M. Morrison, A. W. Michaels, D. R. Phillips and S. Choi, Life span of erythrocyte membrane protein, Nature 248:763 (1974).

    Article  PubMed  CAS  Google Scholar 

  54. R. S. Schwartz, A. C. Rybicki, R. Health and B. H. Lubin, Protein 4.1 in sickle erythrocytes-Evidence for oxidative damage, J. Biol. Chem. 262:15666 (1987).

    PubMed  CAS  Google Scholar 

  55. L. C. Wolfe, A. M. Byrne and S. E. Lux, Molecular defect in the membrane skeleton of blood bank-stored red cells, J. Clin. Invest. 78:1681 (1986).

    Article  PubMed  CAS  Google Scholar 

  56. G. M. Wagner, D. T-Y. Chiu, J-H. Qju, R. H. Heath and B. H. Lubin, Spectrin oxidation correlates with membrane vesciculation in stored RBCs, Blood 69:1777 (1987).

    PubMed  CAS  Google Scholar 

  57. N. Brot, L. Weissbach, J. Werth and H. Weissbach, Enzymatic reduction of protein-bound methionine sulfoxide, Proc. Natl. Acad. Sci. USA 78:2155 (1981).

    Article  PubMed  CAS  Google Scholar 

  58. A. Spector, R. Scotto, H. Weissbach and N. Brot, Lens methionine sulfoxide reductase, Biochem. Biophys. Res. Commun. 108:429 (1982).

    Article  PubMed  CAS  Google Scholar 

  59. M. M. B. Kay, S. R. Goodman, K. Sorensen, C. F. Whitfield, P. Wong, L. Zaki and V. Rudloff, Senescent cell antigen is immunologically related to band 3, Proc. Natl. Acad. Sci. USA 80:1631 (1983).

    Article  PubMed  CAS  Google Scholar 

  60. M. M. B. Kay, Localization of senescent cell antigen on band 3, Proc. Natl. Acad. Sci. USA 81:5753 (1984).

    Article  PubMed  CAS  Google Scholar 

  61. H. Mueller and H. U. Lutz, Binding of autologous IgG to human red blood cells before and after ATP-depletion — Selective exposure of binding sites (autoantigens) on spectrin-free vesicles, Biochim. Biophys. Acta 729:249 (1983).

    Article  CAS  Google Scholar 

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Brovelli, A. et al. (1991). Conformational Changes and Oxidation of Membrane Proteins in Senescent Human Erythrocytes. In: Magnani, M., De Flora, A. (eds) Red Blood Cell Aging. Advances in Experimental Medicine and Biology, vol 307. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5985-2_6

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  • DOI: https://doi.org/10.1007/978-1-4684-5985-2_6

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