Aging of cell membrane molecules: Band 3 and senescent cell antigen in neural tissue

  • M. M. B. Kay
  • J. Hughes
  • I. Zagon
Part of the Veröffentlichungen aus der Geomedizinischen Forschungsstelle der Heidelberger Akademie der Wissenschaften book series (HD AKAD, volume 1990 / 1990/2)


Senescent cell antigen (SCA), an aging antigen, is a protein that appears on old cells and acts as a specific signal for the termination of that cell by initiating the binding of IgG autoantibody and subsequent removal by phagocytes (Kay 1975, 1978, 1981, 1984; Kay et al. 1986 and 1989; Hebber and Miller 1984; diner et al. 1986; Glass et al. 1983 and 1985; Bartosz et al. 1982a and b; Khansari et al. 1983; Khansari and Fudenberg 1983; Alderman et al. 1980; Tannert 1978; Wegner et al 1980; Walker et al. 1984; Kay et al 1983; Lutz et al. 1984; Muller and Lutz 1983). This appears to be a general physiologic process for removing senescent and damaged cells in mammals and other vertebrates (Kay 1981). Although the initial studies were done using human erythrocytes as a model senescent cell antigen has been found on all cells examined (Kay 1981). the aging antigen itself is generated by the degradation of an important structural and transport membrane molecule, protein band 3 (Kay 1984). Besides its role in the removal of senescent and damaged cells, senescent cell antigen also appears to be involved in the removal of erythrocytes in clinical hemolytic anemias (Hebbel and Miller 1984; Kay et al. 1989) and the removal of malaria-infected erythrocytes (Friedman et al. 1985; Dluzewski et al 1986). Oxidation generates senescent cell antigen in situ (Kay et al. 1986).


Cellular Aging Anion Transport Senescent Erythrocyte Cell Membrane Molecule Aging Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alderman EM, Fudenberg HH, Lovins RE (1980) Binding of immunoglobulin classes to subpopulations of human red blood cells separated by density-gradient centrifugation. Blood 55: 817–822PubMedGoogle Scholar
  2. Alpert SL,Kopito RR, Libresco SM, Lodish HF (1988) Cloning and characterization of a murine band 3-related cDNA from kidney and from a lymphoid cell line. J Biol Chem 263: 17092–17099Google Scholar
  3. Bartosz G, Sosynski M, Kredziona J (1982) A ng of the erythrocyte.Google Scholar
  4. Accelerated red cell membrane aging in Down’s syndrome. Cell Biolint Rep 6: 73–77Google Scholar
  5. Bartosz G Sosynski M, Wasilewski A (1982) Aging of the erythrocyte XVII. Binding of autologous immunoglobin. Mech Aging Dev 20: 223–232Google Scholar
  6. Bennett GD, Kay MMB (1981) Homeostatic removal of senescent murine erythrocytes by splenic macrophages. Exp Hematol 9: 297–307PubMedGoogle Scholar
  7. Bennett V (1979) Immunoreactive forms of human erythrocyte ankyrin areresent in diverse cells. Nature Lond 281: 597–599PubMedCrossRefGoogle Scholar
  8. Bennett V, Stenbuck PJ (1980) Association between ankyrin and the cytoplasmic domain of band 3 isolated from the human erythrocyte membrane. J Biol Chem 255: 6424–6432PubMedGoogle Scholar
  9. Bjerrum PJ, Wieth JO, Minakami S (1983) Selective phenyllyoxalation of functionally essential arginyl residues in the erythrocyte anion transport protein. J Gen Physiol 81: 453–484PubMedCrossRefGoogle Scholar
  10. Bolton AE, Hunter WM (1973) The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J 133: 529–539PubMedGoogle Scholar
  11. Bosman GJCGM, Kay MMB (1988) Erythrocyte aging: A comparison of model systems for simulating cellular aging in vitro. Blood Cells 14: 19–35Google Scholar
  12. Branch DR Gallagher MT, Mison AP Sy Siok Hian AL, Petz LD (1984) In vitro determination of red cell afloantibody significance using an assay of monocyte-macrophage interaction with sensitized erythrocytes. Br J Haematol 56: 19–29Google Scholar
  13. Cabantchik ZI, Rothstein A (1972) The nature of the membrane sites controlling anion permeability of human red blood cells as determined by studies with disulfonic stilbene derivitives. J Membr Biol 10: 311–332PubMedCrossRefGoogle Scholar
  14. Cabantchik ZI, Rothstein A (1974) Membrane proteins related to anion permeability of human red blood cells. J Memb Biol 15: 207–226CrossRefGoogle Scholar
  15. Cheung MO, Lo TCY (1984) Hexose transport in plasma membrane vesicles of rat myoblast L6. Can J Biochem Cell Biol 62: 1–217–1227Google Scholar
  16. Colowick SP, Womack FC (1969) Binding of diffusible molecules by macromolecules: rapid measurement by rate of dialysis. J Biol Chem 244: 774–777PubMedGoogle Scholar
  17. Cox JV, Lazarides E (1988) Alternative primary structures in the transmembrane domain of the chicken erythroid anion transporter. Mol Cell Biol 8: 1327–1335PubMedGoogle Scholar
  18. Craik ED Reithmeier R (1981). J Appl Physiol 50: 265–271Google Scholar
  19. Demuth OR, Showe LC Ballantine M Palumbo A, Fraser PJ, Cioe L, Rovera G, Curtis PJ (1986) Cloning and structural characterization of a human non-erythroid band 3-like protein. Embo Journal 5: 1205–1214Google Scholar
  20. Dix JA, Verkman AS, Solomon AK (1986) Binding of chloride and a disulfonic stilbene transport inhibitor to red cell band 3. J. Membr. Biol. 89: 211–223Google Scholar
  21. Dluzewski AR Rangachari K, Tanner MJ, Anstee DJ, Wilson RJ, Gratzer WB (1986) inhibition of malarial invasion by intracellular antibodies against intrinsic membrane proteins in the red cell. Parasitolog~ryry 93: 427–431Google Scholar
  22. Elgavish A, Smith JB Pillon DJ, Mezon E (1985) Sulfate transport in human Iun fibroblasts (IMR-90). J Cell Physiol 125: 243–250PubMedCrossRefGoogle Scholar
  23. FalkeJJ, Kanes KJ, Chan SI (1985) The minimal structure containing the band 3 anion transport site. A 35CI NMR study. J Biol Chem 260: 13294–13303Google Scholar
  24. Friedman MJ, Fukuda M, Laine RA (1985) Evidence for a malarial parasite interaction site on the major transmembrane protein of the human erythrocyte. Science 228: 75–77PubMedCrossRefGoogle Scholar
  25. GaczynskaM, Rosin J, Soszynski M, Bartosz G (1986) Proteolytic susceptibility of membrane proteins during erythrocyte aging. Mech Agin_g Dev 35: 109–121CrossRefGoogle Scholar
  26. Glass GA, Gershon D, Gershon H (1985) Some characteristics of the human erythrocyte as a function of donor and cell age. Exp Hematol 13: 1122–1126PubMedGoogle Scholar
  27. Glass GA, Gershon H, Gershon D (1983) The effect of donor and cell age on several characteristics of rat erythrocytes. Exp Hematol 11: 987–995PubMedGoogle Scholar
  28. Goodman SR, Shiffer K (1983) The spectrin membrane skeleton of normal and abnormal human erythrocytes: a review. Am J Physiol 244: C121–C141PubMedGoogle Scholar
  29. Hazen-Martin DJ, Pasternack G, Spicer SS, Sens DA (1986) Immunolocalization of band 3 protein in normal and cystic fibrosis skin. J Histochem Cytochem 34: 823–826PubMedCrossRefGoogle Scholar
  30. Hebbel RP, Miller WJ (1984) Phagocytosis of sickle erythrocytes. Immunologic and oxidative determinants of hemolytic anemia. Blood 64: 733–741Google Scholar
  31. Jennings ML, Anderson MP, Monaghan R (1986) Monoclonal antibodies against human erythrocyte band 3 protein. Localization of proteolytic cleavage sites and stilbenedisulfonate-binding lysine residues. J Biol Chem 261: 9002–9010Google Scholar
  32. Jennings ML, Nicknish JS (1984) Erythrocyte band 3rotein: evidence for multiple membrane-crossing segments in the 17p000-dalton chymotryptic fragment. Biochemisfry 23: 6432–6436CrossRefGoogle Scholar
  33. Jennings ML, Passow H (1979) Anion transport across the erythrocyte membrane, in situ proteolysis of band 3 protein, and cross-_inking of proteolytic fragments by 4 4’-diisothiocyano dihydrostilbene2,2’-disulfonate.Biochim Briophys Acta 554: 498–519CrossRefGoogle Scholar
  34. Kay MMB (1975) Mechanism of removal senescent cells by human macrophages in situ. Proc Natl Acad Sci 72: 3521–3525.PubMedCrossRefGoogle Scholar
  35. Kay MMB (1978) Role of physiologic autoantibody in the removal of senescent human red cells. J Supramol Struct 9: 555–567PubMedCrossRefGoogle Scholar
  36. Kay MMB (1981) Isolation of the phagocytosis-inducing IgG-binding antigen on senescent somatic cells. Nature 289: 491–494PubMedCrossRefGoogle Scholar
  37. Kay MMB (1983a) Antigenic changes associated with cellular aging. rogClin Biol Res 133: 65–76Google Scholar
  38. Ka MMB, Goodman S, Sorensen K, Whitfield C Wong P, Zaki L, Rudoloff V 1983b ) The senescent cell antigen is immunologically related to band Proc Natl Acad Sci 80: 1631–1635Google Scholar
  39. Kay MMB (1984) Localization of senescent cell antigen on band 3. Proc Nat Acad Sci 81: 5753–5757PubMedCrossRefGoogle Scholar
  40. Kay MMB.(1985) Aging of cell membrane molecules leads to appearance of an aging antigen and removal of senescent cells. Gerontology 31: 215–235PubMedCrossRefGoogle Scholar
  41. Kay MMB, Sorensen K, Wong P, Bolton P (1982) Antigenicity, storage and aging: Physiologic autoantibodies to cell membrane and serum proteins and the senescent cell antigen. Mol Cell Biochem 49: 65–85PubMedCrossRefGoogle Scholar
  42. Kay, M.M.B. (1986) Senescent cell antigen: A red cell aging antigen. n: Red Cell Antigens and Antibodies, edited by Garratty, G. Arlin von,VA: American Association of Blood Banks,, pp. 35–82.Google Scholar
  43. Kay, M.M.B. (1988) Immunologic techniques for analyyzing red cell membrane_proteins. In: Methods in Hematology: Red Cell Membranes, edited by Shohet, S. and Mohandas, N. New York: Churchill Livingston, Inc. pp. 135–170.Google Scholar
  44. Kay MMB, Bosman IX, Notter M, Coleman P (1988b) Life and death of neurons: The role of senescent cell antigen. Ann NY Acad Sci 521: 155–169PubMedCrossRefGoogle Scholar
  45. Kay, M.M.B. (1989a) Molecular aging of membrane molecules and cellular removal. In: Biomedical Advances in Aging, edited by Goldstein, A. New York: Plenum Press pp.Google Scholar
  46. Kay MMB, Bosman GJCGM Johnson G, Beth A (1988) Band 3 polymers and a gregates and hemoglobin precipitates in red cell aging. Blood ells 14: 275–289Google Scholar
  47. Kay MMB, Bosman GJCGM, Lawrence C (1988) Functional topography of band 3: A specific structural alteration linked to functional aberrations in human erythrocytes. Proc Natl Acad Sci 85: 492–496PubMedCrossRefGoogle Scholar
  48. Kay MMB, Bosman GJCGM, Shapiro SS, Bendich A, Bassel PS (1986) 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: 2463–2467PubMedCrossRefGoogle Scholar
  49. Kay MMB, Flowers N Goodman J, Bosman GJCGM (1989) Alteration in membrane protein band 3 associated with accelerated erythrocyte a n. Proc atl Acad Sci 86: 5834–5838CrossRefGoogle Scholar
  50. Kay MMB, Flowers N Goodman J, Bosman GJCGM (1989) Alteration in membrane protein band 3 associated with accelerated erythrocyte a n. Proc atl Acad Sci 86: 5834–5838CrossRefGoogle Scholar
  51. Kay MMB (1989b) Red cell aging: Senescent cell antigen, band 3 and band 3 mutations associated with cellular dysfunction. Proc Clin Biol Res 319: 199–217Google Scholar
  52. Kay MMB, Tracey CM, Goodman JR, Cone JC, Bassel PS (1983a) Polypeptides immunologically related to erythrocyte band 3 are present in nucleated somatic cells. Proc NatlAcad Sci 80: 6882–6886CrossRefGoogle Scholar
  53. Kay MMB (1989c) Senescent cell antigen band 3, and band 3 mutations in cellular aging Biomed biochim Acta (in Kellokumpu S, Neff L, Jams-ellokum u S )Google Scholar
  54. Kopito R, Baron R (1988) A 115-kB polypeptide immunologically related to erythrocyte band 3 is present in Golgi membranes. Science 242: 1308–1311PubMedCrossRefGoogle Scholar
  55. Khansari N, Fudenberg HH (1983) Immune elimination of autologous senescent erythrocytes by Kupffer cells in vivo. Cell Immunol 80: 426–430PubMedCrossRefGoogle Scholar
  56. Khansari N, Springer GF, Merler E, Fudenberg HH (1983) Mechanisms for the removal of senescent human erythrocytes from circulation: specificity of the membrane-bound immunoglobulin G. J Mech Aging Dev 21: 49–58CrossRefGoogle Scholar
  57. Knauf PA (1979) Erythrocyte anion exchange and the band 3 protein: Transport kinetics and molecular structure. Curr Top Membr Transp 12: 249–363Google Scholar
  58. Kopito RR, Lodish HF (1985) Structure of the murine anion exchange protein. J Cell Biochem 29: 1–17PubMedCrossRefGoogle Scholar
  59. Kurycki K, Shull G (1989) Primary structure of the rat kidney band 3 anion exchange protein deduced from a cDNA. J Biol Chem 264: 8185–8192Google Scholar
  60. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, Lond 227: 680–685CrossRefGoogle Scholar
  61. Lowry OR, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275PubMedGoogle Scholar
  62. Lutz HU, Flepp R Stringaro-Wipf G (1984) 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: 2160–2618Google Scholar
  63. Muller H,Lutz HU (1983) 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 Bio hyys Acta 729: 249–257CrossRefGoogle Scholar
  64. Nigg E, Cherry RJ (1979) Dimeric association of band 3 in the erythrocyte membrane demonstrated by protein diffusion measurements. Nature 277: 493–494PubMedCrossRefGoogle Scholar
  65. Saitoh T Dobkins K (1986) Protein kinase C in human brain and its inhibition by calmodulin. Brain Res Bull 379: 196–199Google Scholar
  66. Saitoh T Oswald R Wennogle LP Changeux JP (1980) Conditions for the selective labelling of the 66 b00 dalton chain of the acetylcholine receptor by the covalent non-competitive blocker 5-azido-[3H trimethisoquin. FEBS Lett 116: 30–36CrossRefGoogle Scholar
  67. Scatchard G. Ann. NY Acad Sci (1949) 51: 660–666CrossRefGoogle Scholar
  68. Schnell KF, Gerhardt S, Schoppe-Fredenburg A (1977) Kinetic characteristics of the sulfate self-exchange in human red blood cells and red blood cell ghosts. J Membr Biol 30: 319–350PubMedGoogle Scholar
  69. Schuster VL, Bonsib SM Jennings ML (1986) Two types of collecting duct mitochondria-rich (intercalated) cells: lectin and band 3 cytochemistry. Am J Physiol 251: C347–C355PubMedGoogle Scholar
  70. Ship S, Shami Y, Breuer W, Rothstein A (1977) Synthesis of tritiated 4,4’-diisothiocyano-2 2’-stilbene disulfonic acid ([3H]DIDS)and its covalent reaction with sites related to anion transport in human red blood cells. J Membr Biol 33: 311–324PubMedCrossRefGoogle Scholar
  71. Singer JA Jennings LK Jackson C, Doctker ME, Morrison M, Walker WS (1986) Erythrocyte homeostasis: Antibody-mediated recognition of the senescent state by macrophages. Proc Natl Acad Sci USA 83: 5498–5501Google Scholar
  72. Steck TL (1974) The organization of proteins in human red blood cell membranes. J Cell Biol 62: 1–19PubMedCrossRefGoogle Scholar
  73. Steck TL (1978) The band 3 protein of the human red cell membrane: A review. J bupramol Struct 8: 311–324CrossRefGoogle Scholar
  74. Steiner JP Bennett V (1988) Ankyrin-independent membrane protein-binding sites for brain and erythrocyte spectrin. J Biol Chem 263, No. 28: 14417–14425PubMedGoogle Scholar
  75. Tanner MJA, Martin PG, High S (1988) The complete amino acid sequence of the human erythrocyte membrane anion-transport protein deduced from the cDNA sequence.Biochem J 256: 703–712PubMedGoogle Scholar
  76. Tannert CH (1978) Untersuchungen zum altern roter blutzellen. (UnPub)Google Scholar
  77. Towbin H, Staehelin T, Gordon,F(1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci 76: 4350–4354Google Scholar
  78. Walker WS, Singer JA, Morrison M, Jackson CW (1984) Preferential phagocytosis of in vivo aged murine red blood cells by a macrophage-like cell line. Br J Haemat 58: 259–266CrossRefGoogle Scholar
  79. Wegner G, Tannert CH, Maretzki D, Schossler W, Strauss D ( 1980 IgG bindin to glucose depleted and preserved erythrocytes. 9th Int ymp Struct unction Erythroid Cells, Berlin, GDR 57Google Scholar
  80. Wieth JO Andersen OS, Brahm J, Bjerrum PJ Borders CL Jr (1982) Chloride-bicarbonate exchangce in red blood cells: physiology of transport and chemical modification of binding sites. Philos-Trans R Soc Lond (Biol) 299: 383–399CrossRefGoogle Scholar
  81. Yam P, Petz LD Spath P (1982) Detection of IgG sensitization of red cells with 1251 staphylococcal protein A. Am Journal Hematol 12: 337–346CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • M. M. B. Kay
    • 1
    • 2
  • J. Hughes
    • 2
  • I. Zagon
    • 3
  1. 1.Department of MedicineTexas A&M University College of MedicineUSA
  2. 2.Teague Veterans’ Center TempleUSA
  3. 3.Department of AnatomyPennsylvania State UniversityHersheyUSA

Personalised recommendations