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Journal of Protein Chemistry

, Volume 14, Issue 8, pp 633–644 | Cite as

Interaction of synthetic Alzheimerβ-protein-derived analogs with aqueous aluminum: A low-field27Al NMR investigation

  • Sandip B. Vyas
  • Lawrence K. Duffy
Article

Abstract

Synthetic peptides corresponding to the soluble Alzheimerβ-protein, i.e., β1–40 and β6-25, were utilized to investigate the association of aluminum using low-field27Al nuclear magnetic resonance (NMR) spectroscopy and reversed-phase high-performance liquid chromatography (RP-HPLC). Addition of β1-40 or β6-25 to aqueous Al3+ gives rise to a27Al NMR signal corresponding to the association of Al3+ with the peptides; this effect is not easily reversed by EDTA. Based on the relative intensity of the Al3+-peptide signal between pH 4 and 6, there are at least 4 Al3+ ions associated with each peptide molecule. Microheterogeneity is observed with RP-HPLC on incubating solutions of Al3+ with β1-40 and β6-25. The27Al NMR spectra of chromatographically pure fractions of β1-40 and β6-25 indicate that the peptide-associated Al3+ is released below pH 3.5. We propose that soluble β1-40 provides an anchor for Al3+ to bind, eventually leading to an increased deposition of amyloid in the Alzheimer brain.

Key words

Alzheimerβ-protein aluminum nuclear magnetic resonance spectra reversed-phase high-performance liquid chromatography amyloid 

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References

  1. Akitt, J. W. (1987). InMultinuclear NMR (Mason, J., ed.), Plenum Press, New York.Google Scholar
  2. Akitt, J. W., and Milic, N. B. (1984).Chem. Soc. Dalton Trans. 1984, 981.CrossRefGoogle Scholar
  3. Anderson, K. K., Perez, G. L., Fisher, G. H., and Man, E. H. (1990).Neurosci. Res. Commun. 6, 45.Google Scholar
  4. Arispe, N., Rojas, E., and Pollard, H. B. (1993).Proc. Natl. Acad. Sci. USA 90, 567.PubMedGoogle Scholar
  5. Atherton, E., and Sheppard, R. C. (1985).J. Chem. Soc. Chem. Commun. 3, 165.Google Scholar
  6. Bottero, J. Y., Cases, J. M., Fiessinger, F., and Poirer, J. E. (1980).J. Phys. Chem. 84, 2933.Google Scholar
  7. Candy, J. M., Oakley, A. E., Klinowski, J., Carpenter, T. A., Perry, R. H., Atack, J. R., Perry, E. K., Blessed, G., Fairbairn, A., and Edwardson, J. A. (1966).Lancet i, 354.Google Scholar
  8. Candy, J. M., McArthur, F. K., Oakley, A. E., Taylor, G. A., Chen, C. P. L.-H., and Mountfort, S. A. (1992).J. Neurol. Sci. 107, 210.PubMedGoogle Scholar
  9. Charlet, Ph., Deloume, J. P., Duc, G., and Thomas-David, G. (1984).Bull. Soc. Chim. 7–8, 1222.Google Scholar
  10. Crapper, D. R., Krishnan, S. S., and Dalton, A. J. (1973).Science 180, 511.PubMedGoogle Scholar
  11. Exley, C., Price, N. C., Kelly, S. M., and Birchall, J. D. (1993).FEBS Lett. 324, 293.PubMedGoogle Scholar
  12. Farnsworth, V., Carson, W., and Krutzsch, H. (1991).Peptide Res. 4, 245.Google Scholar
  13. Fasman, G. D., and Moore, C. D. (1994).Proc. Natl. Acad. Sci. USA 91, 11232.PubMedGoogle Scholar
  14. Fatemi, S. J., Williamson, D. J., and Moore, G. R. (1992).J. Inorg. Biochem. 46, 35.Google Scholar
  15. Glenner, G. G., and Wong, C. W. (1984).Biochem. Biophys. Res. Commun. 120, 885.PubMedGoogle Scholar
  16. Gotham, S. M., Fryer, P. J., and Paterson, W. R. (1988).Anal. Biochem. 173, 353.PubMedGoogle Scholar
  17. Hirano, A., Malamud, N., and Kurland, L. T. (1961).Brain 84, 662.PubMedGoogle Scholar
  18. Hollósi, M., Ürge, L., Perczel, A., Kajtár, J., Teplan, I., Ötvös, L., Jr., and Fasman, G. D. (1992).J. Mol. Biol. 223, 673.PubMedGoogle Scholar
  19. Hollosi, M., Shen, Z. M., Perczel, A., and Fasman, G. D. (1994).Proc. Natl. Acad. Sci. USA 91, 4902.PubMedGoogle Scholar
  20. Huheey, J. E. (1983). InInorganic Chemistry, Harper and Row, New York.Google Scholar
  21. Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzechik, K.-H., Multhaup, G., Beyreuther, K., and Muller-Hill, B. (1987).Nature 325, 733.PubMedGoogle Scholar
  22. Katz, R., Terry, R. D., and Bick, K. L. (1978). InAlzheimer's Senile Dementia and Related Disoreders, Raven Press, New York.Google Scholar
  23. Kawahara, M., Muromato, K., Kobayashi, K., Mori, H., and Kuroda, Y. (1994).Biochem. Biophys. Res. Commun. 198, 531.PubMedGoogle Scholar
  24. Kragten, J. (1978). InAtlas of Metal-Ligand Equilibria in Aqueous Solutions, Vol. 3, Halstead Press, New York.Google Scholar
  25. Lang, E., Szendrei, G. I., Elekes, I., Lee, V. M.-Y., and Otvos, L., Jr. (1992).Biochem. Biophys. Res. Commun. 182, 63.PubMedGoogle Scholar
  26. Lee, V. M.-Y., Balin, B. J., Otvos, L., Jr., and Trojanowski, L. (1991).Science 251, 675.PubMedGoogle Scholar
  27. Mahurkar, S. D., Dhar, S. K., Salta, S., Meyers, L., Jr., Smith, E. C., and Dunea, G. (1973).Lancet 1, 1412.PubMedGoogle Scholar
  28. Mantyh, P. W., Ghilardi, J. R., Rogers, S., DeMaster, E., Allen, C. J., Stimson, E. R., and Maggio, J. E. (1993).J. Neurochem. 61, 1171.PubMedGoogle Scholar
  29. Martin, R. B. (1986).Clin. Chem. 32, 1797.PubMedGoogle Scholar
  30. Masters, C. L., Simms, C., Weidemann, N. A., Multhaup, G., McDonald, B. L., and Beyreuther, K. (1985).Proc. Natl. Acad. Sci. USA 82, 4245.PubMedGoogle Scholar
  31. Matsudaira, P. (1987).J. Biol. Chem. 262, 10035.PubMedGoogle Scholar
  32. Ott, S. M., Maloney, N. A., Coburn, J. W., Alfrey, A. C., and Sherrard, D. J. (1982).N. Engl. J. Med. 307, 709.PubMedGoogle Scholar
  33. Otvos, L., Jr., Hollosi, M., Perczel, A., Dietschold, B., and Fasman, G. D. (1988).J. Protein Chem. 7, 365.PubMedGoogle Scholar
  34. Perl, D. P. (1985).Environ. Health Perspect. 63, 149.PubMedGoogle Scholar
  35. Perl, D., and Brody, A. (1980).Science 208, 297.PubMedGoogle Scholar
  36. Prelli, F., Castano, E. M., Glenner, G. G., and Frangione, B. (1988).J. Neurochem. 51, 648.PubMedGoogle Scholar
  37. Prior, J. C., Cameron, E. C., Knickerbocker, J., Sweeney, V. P., and Suchowersky, O. (1982).Am. J. Med. 72, 33.PubMedGoogle Scholar
  38. Roher, A. E., Lowenson, J. D., Clarke, S., Wolkow, C., Wang, R., Cotter, R. J., Reardon, I. M., Zurcher-Neely, H. A., Heinriksson, R. L., Ball, M. J., and Greenburg, B. D. (1993).J. Biol. Chem. 268, 3072.PubMedGoogle Scholar
  39. Schuurmans-Stekhoven, J. H., Renkawek, K., Otte-Höller, I., and Stols, A. (1990).Neurosci. Lett. 119, 71.PubMedGoogle Scholar
  40. Scott, M. G., Crimmins, D. L., McCourt, D. W., Tarrand, J. J., Eyerman, M. C., and Nahm, M. H. (1988).Biochem. Biophys. Res. Commun. 155, 1353.PubMedGoogle Scholar
  41. Selkoe, D. J. (1995).J. NIH Res. 7, 57.Google Scholar
  42. Seubert, P., Vigo-Pelfry, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schlossmacher, M., Whaley, J., Swindlehurst, C., McCormack, R., Wolfert, R., Selkoe, D. J., Lieberburg, I., and Schenk, D. (1992).Nature 359, 325.PubMedGoogle Scholar
  43. Shapira, R., Austin, G. E., and Mirra, S. S. (1988).Neurochem. 50, 69.Google Scholar
  44. Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M.et al. (1992).Science 258, 126.PubMedGoogle Scholar
  45. Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., and Klenk, D. C. (1985).Anal. Biochem. 150, 76.PubMedGoogle Scholar
  46. Stanhope, J. M., Brody, J. A., and Morris, C. E. (1972).Int. J. Epidemiol. 1, 199.PubMedGoogle Scholar
  47. Vyas, S. B., and Duffy, L. K. (1995).Biochem. Biophys. Res. Commun. 206, 718.PubMedGoogle Scholar
  48. Wehrli, F. X., and Wehrli, S. (1981).J. Magn. Reson. 44, 197.Google Scholar
  49. Wisniewski, H., Terry, R. D., and Hirano, A. (1990).J. Neuropathol. Exp. Neurol. 29, 163.Google Scholar

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Sandip B. Vyas
    • 1
  • Lawrence K. Duffy
    • 1
  1. 1.Department of Chemistry and Biochemistry and Institute of Arctic BiologyUniversity of Alaska FairbanksFairbanks

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