Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Nov 1;89(21):10075–10078. doi: 10.1073/pnas.89.21.10075

Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor.

J D Buxbaum 1, M Oishi 1, H I Chen 1, R Pinkas-Kramarski 1, E A Jaffe 1, S E Gandy 1, P Greengard 1
PMCID: PMC50280  PMID: 1359534

Abstract

Activation of protein kinase C by phorbol esters is known to accelerate the processing and secretion of the beta/A4 amyloid protein precursor. We have now examined various first messengers that increase protein kinase C activity of target cells for their ability to affect beta/A4 amyloid protein precursor metabolism. Acetylcholine and interleukin 1, which are altered in Alzheimer disease, were shown to increase processing of the beta/A4 amyloid protein precursor via the secretory cleavage pathway. Cholinergic agonists stimulated secretion in human glioma and neuroblastoma cells as well as in PC12 cells transfected with the M1 receptor, while interleukin 1 stimulated secretion in human endothelial and glioma cells.

Full text

PDF
10077

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altstiel L. D., Sperber K. Cytokines in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 1991;15(4):481–495. doi: 10.1016/0278-5846(91)90023-t. [DOI] [PubMed] [Google Scholar]
  2. Biedler J. L., Helson L., Spengler B. A. Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res. 1973 Nov;33(11):2643–2652. [PubMed] [Google Scholar]
  3. Buxbaum J. D., Gandy S. E., Cicchetti P., Ehrlich M. E., Czernik A. J., Fracasso R. P., Ramabhadran T. V., Unterbeck A. J., Greengard P. Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation. Proc Natl Acad Sci U S A. 1990 Aug;87(15):6003–6006. doi: 10.1073/pnas.87.15.6003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cacabelos R., Barquero M., García P., Alvarez X. A., Varela de Seijas E. Cerebrospinal fluid interleukin-1 beta (IL-1 beta) in Alzheimer's disease and neurological disorders. Methods Find Exp Clin Pharmacol. 1991 Sep;13(7):455–458. [PubMed] [Google Scholar]
  5. Caporaso G. L., Gandy S. E., Buxbaum J. D., Greengard P. Chloroquine inhibits intracellular degradation but not secretion of Alzheimer beta/A4 amyloid precursor protein. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2252–2256. doi: 10.1073/pnas.89.6.2252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Caporaso G. L., Gandy S. E., Buxbaum J. D., Ramabhadran T. V., Greengard P. Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3055–3059. doi: 10.1073/pnas.89.7.3055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Donnelly R. J., Friedhoff A. J., Beer B., Blume A. J., Vitek M. P. Interleukin-1 stimulates the beta-amyloid precursor protein promoter. Cell Mol Neurobiol. 1990 Dec;10(4):485–495. doi: 10.1007/BF00712843. [DOI] [PubMed] [Google Scholar]
  8. Esch F. S., Keim P. S., Beattie E. C., Blacher R. W., Culwell A. R., Oltersdorf T., McClure D., Ward P. J. Cleavage of amyloid beta peptide during constitutive processing of its precursor. Science. 1990 Jun 1;248(4959):1122–1124. doi: 10.1126/science.2111583. [DOI] [PubMed] [Google Scholar]
  9. Gandy S., Czernik A. J., Greengard P. Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca2+/calmodulin-dependent protein kinase II. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6218–6221. doi: 10.1073/pnas.85.16.6218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gardella J. E., Ghiso J., Gorgone G. A., Marratta D., Kaplan A. P., Frangione B., Gorevic P. D. Intact Alzheimer amyloid precursor protein (APP) is present in platelet membranes and is encoded by platelet mRNA. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1292–1298. doi: 10.1016/s0006-291x(05)80927-1. [DOI] [PubMed] [Google Scholar]
  11. Glenner G. G., Wong C. W. Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1131–1135. doi: 10.1016/0006-291x(84)91209-9. [DOI] [PubMed] [Google Scholar]
  12. Glenner G. G., Wong C. W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984 May 16;120(3):885–890. doi: 10.1016/s0006-291x(84)80190-4. [DOI] [PubMed] [Google Scholar]
  13. Goldgaber D., Harris H. W., Hla T., Maciag T., Donnelly R. J., Jacobsen J. S., Vitek M. P., Gajdusek D. C. Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7606–7610. doi: 10.1073/pnas.86.19.7606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldgaber D., Lerman M. I., McBride O. W., Saffiotti U., Gajdusek D. C. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science. 1987 Feb 20;235(4791):877–880. doi: 10.1126/science.3810169. [DOI] [PubMed] [Google Scholar]
  15. Griffin W. S., Stanley L. C., Ling C., White L., MacLeod V., Perrot L. J., White C. L., 3rd, Araoz C. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7611–7615. doi: 10.1073/pnas.86.19.7611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kang J., Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Multhaup G., Beyreuther K., Müller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987 Feb 19;325(6106):733–736. doi: 10.1038/325733a0. [DOI] [PubMed] [Google Scholar]
  18. Kitaguchi N., Takahashi Y., Tokushima Y., Shiojiri S., Ito H. Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature. 1988 Feb 11;331(6156):530–532. doi: 10.1038/331530a0. [DOI] [PubMed] [Google Scholar]
  19. Masters C. L., Simms G., Weinman N. A., Multhaup G., McDonald B. L., Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245–4249. doi: 10.1073/pnas.82.12.4245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mönning U., König G., Prior R., Mechler H., Schreiter-Gasser U., Masters C. L., Beyreuther K. Synthesis and secretion of Alzheimer amyloid beta A4 precursor protein by stimulated human peripheral blood leucocytes. FEBS Lett. 1990 Dec 17;277(1-2):261–266. doi: 10.1016/0014-5793(90)80861-c. [DOI] [PubMed] [Google Scholar]
  21. Ponte P., Gonzalez-DeWhitt P., Schilling J., Miller J., Hsu D., Greenberg B., Davis K., Wallace W., Lieberburg I., Fuller F. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature. 1988 Feb 11;331(6156):525–527. doi: 10.1038/331525a0. [DOI] [PubMed] [Google Scholar]
  22. Price D. L. New perspectives on Alzheimer's disease. Annu Rev Neurosci. 1986;9:489–512. doi: 10.1146/annurev.ne.09.030186.002421. [DOI] [PubMed] [Google Scholar]
  23. Refolo L. M., Salton S. R., Anderson J. P., Mehta P., Robakis N. K. Nerve and epidermal growth factors induce the release of the Alzheimer amyloid precursor from PC 12 cell cultures. Biochem Biophys Res Commun. 1989 Oct 31;164(2):664–670. doi: 10.1016/0006-291x(89)91511-8. [DOI] [PubMed] [Google Scholar]
  24. Robakis N. K., Ramakrishna N., Wolfe G., Wisniewski H. M. Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4190–4194. doi: 10.1073/pnas.84.12.4190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schubert D., Jin L. W., Saitoh T., Cole G. The regulation of amyloid beta protein precursor secretion and its modulatory role in cell adhesion. Neuron. 1989 Dec;3(6):689–694. doi: 10.1016/0896-6273(89)90237-7. [DOI] [PubMed] [Google Scholar]
  26. Sisodia S. S., Koo E. H., Beyreuther K., Unterbeck A., Price D. L. Evidence that beta-amyloid protein in Alzheimer's disease is not derived by normal processing. Science. 1990 Apr 27;248(4954):492–495. doi: 10.1126/science.1691865. [DOI] [PubMed] [Google Scholar]
  27. Smith R. P., Higuchi D. A., Broze G. J., Jr Platelet coagulation factor XIa-inhibitor, a form of Alzheimer amyloid precursor protein. Science. 1990 Jun 1;248(4959):1126–1128. doi: 10.1126/science.2111585. [DOI] [PubMed] [Google Scholar]
  28. Suzuki T., Nairn A. C., Gandy S. E., Greengard P. Phosphorylation of Alzheimer amyloid precursor protein by protein kinase C. Neuroscience. 1992 Jun;48(4):755–761. doi: 10.1016/0306-4522(92)90264-3. [DOI] [PubMed] [Google Scholar]
  29. Tanzi R. E., Gusella J. F., Watkins P. C., Bruns G. A., St George-Hyslop P., Van Keuren M. L., Patterson D., Pagan S., Kurnit D. M., Neve R. L. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science. 1987 Feb 20;235(4791):880–884. doi: 10.1126/science.2949367. [DOI] [PubMed] [Google Scholar]
  30. Tanzi R. E., McClatchey A. I., Lamperti E. D., Villa-Komaroff L., Gusella J. F., Neve R. L. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature. 1988 Feb 11;331(6156):528–530. doi: 10.1038/331528a0. [DOI] [PubMed] [Google Scholar]
  31. Weidemann A., König G., Bunke D., Fischer P., Salbaum J. M., Masters C. L., Beyreuther K. Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein. Cell. 1989 Apr 7;57(1):115–126. doi: 10.1016/0092-8674(89)90177-3. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES