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Proteolytic activity in brains of rabbits treated with aluminum

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Abstract

Aluminum injection in rabbits leads to neurofibrillary changes which are at light microscopic level similar to those found in Alzheimer's disease. We used this animal model to see whether changes in proteolytic activity occur that may affect protein degradation in the altered neurofibrillary structure. Rabbits were injected via the cisterna magna with aluminum chloride, and after ten days tissue was excised from the spinal cord, hippocampus, occipital lobe, and cerebellum. Sections from the hippocampus and spinal cord were examined for neurofibrillary changes; enzyme activity was measured in all four areas. The enzymes studied were cathepsins A, B, and D, and the angiotensin-converting enzyme. No significant differences could be established in enzymatic activity in aluminum-injected animals compared to controls. However, a significant decrease in Triton-soluble proteins was observed in the treated animals, which correlated with changes in neurofibrillary structure. This decrease was most noticeable in the spinal cord (from 16.6 to 12.5 mg/g).

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References

  1. Zimmerman, U.-J.P., andSchlaepfer, W. W. 1982. Characterization of a brain calciumactivated protease that degrades neurofilament protein. Biochemistry 21:3977–3983.

    PubMed  Google Scholar 

  2. Schlaepfer, W. W. 1983. Neurofilaments and the abnormal filaments of Alzheimer's disease. Pages 107–115, in Katzman, R. (ed.), Banbury Report 15, Biological Aspects of Alzheimer's Disease, Cold Spring Harbor Laboratory, New York.

    Google Scholar 

  3. Selkoe, D. J., Abraham, C., andIhara, Y. 1982. Brain transglutaminase: In vitro crosslinking of human neurofilament proteins into insoluble polymers. Proc. Natl. Acad. Sci. USA 79:6070–6074.

    PubMed  Google Scholar 

  4. Iqbal, K., Zaidi, T., Thompson, C. H., Merz, P. A., andWisniewski, H. M. 1984. Alzheimer paired helical filaments: Bulk isolation, solubility, and protein composition. Acta Neuropathol. (Berl) 62:167–177.

    Google Scholar 

  5. Grundke-Iqbal, I., Iqbal, K., Tung, Y.-C., andWisniewski, H. M. 1984. Alzheimer paired helical filaments: Immunochemical identification of polypeptides. Acta Neuropathol. (Berl) 62:259–267.

    Google Scholar 

  6. Sajdel-Sulkowska, E. M., andMarotta, C. A. 1984. Alzheimer's disease brain. Alterations in RNA levels and in a ribonuclease-inhibitor complex. Science 225:947–949.

    PubMed  Google Scholar 

  7. Cammer, W., Bloom, B. R., Norton, W. T., andGordon, S. 1978. Degradation of basic protein in myelin by neutral proteases secreted by stimulated macrophages. A possible mechanism of inflammatory demyelination. Proc. Natl. Acad. Sci. USA 75:1554–1558.

    PubMed  Google Scholar 

  8. Smith, M. E., Chow, S. H., andRolph, R. H. 1981. Partial purification and characterization of neutral proteases in lymph nodes of rats with experimental allergic encephalomyelitis. Neurochem. Res. 6:901–912.

    PubMed  Google Scholar 

  9. Smith, M. E., andAmaducci, L. A. 1982. Observations on the effects of protease inhibitors on the suppression of experimental allergic encephalomyelitis. Neurochem. Res. 7:541–548.

    Google Scholar 

  10. Banik, N. L., Hogan, E. L., Powers, J. M., andWhetstine, L. J. 1982. Degradation of cytoskeletal protein in experimental spinal cord injury. Neurochem. Res. 7:1465–1475.

    PubMed  Google Scholar 

  11. Crapper, D. R., Krishman, S. S., andDalton, A. J. 1973. Brain aluminum distribution in Alzheimer's disease and experimental neurofibrillary degeneration. Science 180:511–513.

    PubMed  Google Scholar 

  12. Crapper, D. R., Krishman, S. S., andQuittkat, S. 1976. Aluminum, neurofibrillary degeneration, and Alzheimer's disease. Brain 99:67–80.

    PubMed  Google Scholar 

  13. Perl, D. P. 1983. Aluminum and Alzheimer's disease: Intraneuronal X-ray spectrometry studies. Pages 425–431,in Katzman, R. (ed.), Banbury Report 15, Biological Aspects of Alzheimer's Disease, Cold Spring Harbor Laboratory, New York.

    Google Scholar 

  14. McDermott, J. R., Smith, A. I., Iqbal, K., andWisniewski, H. M. 1979. Aluminum and Alzheimer's disease. Lancet 2:710.

    Google Scholar 

  15. McDermott, J. R., Smith, A. I., Iqbal, K., andWisniewski, H. M., 1979. Brain aluminum in aging and Alzheimer's disease. Neurology 29:809–814.

    PubMed  Google Scholar 

  16. Markesbery, W. R., Ehmann, W. D., Hossain, T. I. M., Alauddin, M., andGoodin, D. T. 1981. Instrumental neutron activation analysis of brain aluminum in Alzheimer's disease and aging. Ann. Neurol. 10:511–516.

    PubMed  Google Scholar 

  17. Terry, R. D., andPena, C. 1965. Experimental production of neurofibrillary degeneration. Electron microscopy, phosphatase histochemistry and electron probe analysis. J. Neuropathol. Exp. Neurol. 24:200–210.

    PubMed  Google Scholar 

  18. Yates, C. M., Gordon, A., andWilson, H. 1976. Neurofibrillary degeneration induced in the rabbit by aluminum chloride: aluminum neurofibrillary tangles. J. Neuropathol. Appl. Neurobiol. 2:131–144.

    Google Scholar 

  19. Wisniewski, H., Narkiewicz, O., andWisniewski, K. 1967. Topography and dynamics of neurofibrillary degeneration in aluminum encephalopathy. Acta Neuropathol. (Berl) 9:127–133.

    Google Scholar 

  20. Wisniewski, K., Jervis, G. A., Moretz, R. C., andWisniewski, H. M. 1979. Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia. Ann. Neurol. 5:288–294.

    PubMed  Google Scholar 

  21. Wisniewski, H. M., Sturman, J. A., andShek, J. W. 1980. Aluminum chloride induced neurofibrillary changes in the developing rabbit: A chronic animal model. Ann. Neurol. 8:479–490.

    PubMed  Google Scholar 

  22. Benuck, M., Berg, M. J., andMarks, N. 1982. Separate metabolic pathways for Leuenkephalin and Met-enkephalin-Arg6-Phe7 degradation by rat striatal synaptosomal membranes. Neurochem. Int. 4:389–396.

    Google Scholar 

  23. Arregui, A., Perry, E. K., Rossor, M. andTomlinson, B. E. 1982. Angiotensin converting enzyme in Alzheimer's disease: Increased activity in caudate nucleus and cortical areas. J. Neurochem. 38:1490–1492.

    PubMed  Google Scholar 

  24. Marks, N., Sachs, L., andStern, F. 1981. Conversion of Met-enkephalin-Arg6-Phe7 by a purified brain carboxypeptidase (cathepsin A). Peptides 2:159–164.

    PubMed  Google Scholar 

  25. Suhar, A. andMarks, N. 1979. Purification and properties of brain cathepsin B. Eur. J. Biochem. 101:23–30.

    PubMed  Google Scholar 

  26. Banay-Schwartz, M., Bracco, F., DeGuzman, T., andLajtha, A. 1983. Developmental changes in the breakdown of brain tubulin by cerebral cathepsin D. Neurochem. Res. 8:51–61.

    PubMed  Google Scholar 

  27. Piquilloud, Y. A., Reinharz, A., andRoth, M. 1970. Studies on the angiotensin converting enzyme with different substrates. Biochim. Biophys. Acta 206:136–142.

    PubMed  Google Scholar 

  28. Lowry, O. H., Rosebrough, N. J., Farr, A. L., andRandall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.

    PubMed  Google Scholar 

  29. Bowen, D. M., Smith, C. B., andDavison, A. N. 1973. Molecular changes in senile dementia. Brain 96:849–856.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Center for Neurochemistry, The Nathan S. Kline Institute for Psychiatric Research, Ward's Island, 10035, New York, NY

    M. Benuck, K. Iqbal, H. M. Wisniewski & A. Lajtha

  2. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, 10314, Staten Island, NY

    K. Iqbal & H. M. Wisniewski

Authors
  1. M. Benuck
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  2. K. Iqbal
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  3. H. M. Wisniewski
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  4. A. Lajtha
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Benuck, M., Iqbal, K., Wisniewski, H.M. et al. Proteolytic activity in brains of rabbits treated with aluminum. Neurochem Res 10, 729–736 (1985). https://doi.org/10.1007/BF00964531

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