Chromogranins pp 291-298 | Cite as

Chromogranin A Induces a Neurotoxic Phenotype in Brain Microglial Cells

  • Jaroslava Ciesielski-Treska
  • Dominique Aunis
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 482)

Conclusion

Neurodegenerative diseases are characterized by a progressive loss of neurons but the underlying mechanisms are not well understood. Several lines of evidence indicate that neurons and microglial cells cooperate in the initiation and development of toxic signaling pathways. Both cell-surface interactions and released molecules seem to be involved in the process of neuronal degeneration. Our results indicate that CGA, which is up-regulated in many neuropathologies, represents an endogeneous inflammatory molecule responsible for the induction of signalling cascade leading to secretion of neurotoxic factors from microglia (Fig 2).

Keywords

Microglial Cell Senile Plaque Dystrophic Neurites Chromaffin Granule Neurotoxic Factor 
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.
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References

  1. Aardal, S., Helle, K.B., Elsayed, S., Reed, R.K., and Serck-Hanssen, G., 1993, Vasostatins, comprising the N-terminal domain of chromogranin A, suppress tension in isolated human blood vessel segments. J. Neuroendocrinol. 5: 405–412.PubMedGoogle Scholar
  2. Bader, M.F., Taupenot, L., Ulrich, G., Aunis, D., and Ciesielski-Treska, J., 1994, Bacterial lipopolysaccharide triggers the release of Ca++ from intracellular stores in brain macrophagesandchangestheorgansiation of actin, Glia 11: 336–344.CrossRefPubMedGoogle Scholar
  3. Banati, R.B., and Graeber, M.B., 1994, Srveillance, intervention and cytotoxicity, is there a protective role ofmicroglia? Dev. Neurosci. 16: 114–127.PubMedGoogle Scholar
  4. Chao, C.C., Hu, S., and Peterson, P.K., 1995, Glia, cytokines and neurotoxicity. CriticalRev. Neurobiol. 9: 189–205.Google Scholar
  5. Ciesielski-Treska, J., Ulrich, G., and Aunis, D., 1991, Protein kinase C-induced redistribution of the cytoskeleton and phosphorylation of vimentin in cultured brain macrophages. J. Neurosci. Res. 29: 362–378.CrossRefPubMedGoogle Scholar
  6. Ciesielski-Treska, J., Ulrich, G., Taupenot, L., Chasserot-Golaz, S., Corti, A., Aunis, D. and Bader, M.F., 1998, Chromogranin A induces a neurotoxic phenotype in brain microglial cells. J. Biol. Chem. 273: 14339–14346.CrossRefPubMedGoogle Scholar
  7. Dickson, D.W., 1997, The pathogenesis of senile plaques. J. Neuropathol. Exp. Neurol. 56: 321–339.PubMedGoogle Scholar
  8. Drees, B.M., and Hamilton, J.W., 1994, Processing of chromogranin A by bovine parathyroid secretory granules: production and secretion of N-terminal fragments. Endocrinology 134: 2057–2063.CrossRefPubMedGoogle Scholar
  9. Drees, B.M., Rouse, J., Johnson, J., and Hamilton, J.W., 1991, Bovine parathyroid glands secrete a 25-kDa N-terminal fragment of chromogranin A which inhibits parathyroid cell secretion. Endocrinology 129: 3381–3387.PubMedCrossRefGoogle Scholar
  10. El Madjoubi, M., Metz-Boutigue, M.H., Garcia-Sablone, P., Theodosis, D., and Aunis, D., 1996, Immunocytochemical localization of chromogranin A (CGA) in normal and stimulated hypothalamo-neurohypophysial system ofthe rat. J. Neurocytol. 25: 405–416.Google Scholar
  11. Ferrer, I., Marti, E., Tortosa, A., and Blasi, J., 1998, Dystrophic neurites of senile plaques are defective in proteins involved in exocytosis and neurotransmission. J. Exp. Neuropathol. 57: 218–225.Google Scholar
  12. Gasparri, A., Sidoli, A., Perez Sanchez, L., Longhi, R., Siccardi, A.G., Marchisio, P.C., and Corti, A., 1997, Chromogranin A fragments modulate cell adhesion. Identification and characterization ofa pro-adhesive domain. J. Biol. Chem. 272: 20835–20843.CrossRefPubMedGoogle Scholar
  13. Giulian, D., Corpuz, M., Chapman, S., Mansouri, M., and Robertson, C., 1993, Reactive mononuclear phogocytes release neurotoxins after ischemic and traumatic injury to the central nervous system. J. Neurosci. Res. 36: 681–693.CrossRefPubMedGoogle Scholar
  14. Giulian, D., Haverkamp, L.J., Li, J., Karshin, W.L., Yu, J., Tom, D., Li, X., and Kirkpatrick, J.B., 1995, Senile plaques stimulate microglia to release a neurotoxin found in Alzheimer disease. Neurochem. Int. 27: 119–137.CrossRefPubMedGoogle Scholar
  15. Kaul, M., and Lipton, A., 1999, Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc.Natl. Acad. Sci. U.S.A. 96: 8212–8216.CrossRefPubMedGoogle Scholar
  16. Kingham, P.J., Cuzner, M.L., and Pocock, J.M., 1999, Apoptotic pathways mobilized in microglia and neurones as a consequence of chromogranin A-induced microglial activation. J. Neurochem. 73: 538–547.CrossRefPubMedGoogle Scholar
  17. Lugardon, K., Raffner, R., Goumon, Y., Corti, Y., Delmas, A., Bulet, P., Aunis, D., and Metz-Boutigue, M.H., 2000, Antibacterial and antifungal activities of vasostatin-I, the N-terminal fragment of chromogranin A. J. Biol. Chem 275: in press.Google Scholar
  18. Mahata, S.K., Mahata, M., Marksteiner, J., Sperk, G., Fischer-Colbrie, R., and Winkler, H. 1991, Eur. J. Neurosci. 3: 895–904.PubMedGoogle Scholar
  19. McGeer, P.L., Kawamata, T., Walker, D.G., Akiyama, H., Tooyama, I., and McGeer, E.G., 1993, Microglia in degenerative neurological disease. Glia 7: 84–92.CrossRefPubMedGoogle Scholar
  20. Metz-Boutigue, M.H., Garcia-Sablone, P., Hogur-Angeletti, R., and Aunis, D., 1993, Intracellular and extra-cellular processing of chromogranin A. Determination of cleavage sites. Eur. J. Biochem. 217: 247–257.CrossRefPubMedGoogle Scholar
  21. Muñoz, D.G., Kobylinski, L., Henry, D.D., and George, D.H., 1990, Chromogranin A-like immunoreactivity in the human brain: distribution in bulbar medulla and cerebral cortex. Neuroscience 34: 533–543.PubMedGoogle Scholar
  22. Muñoz, D.G., 1991, Chromogranin A-like immunoreactive neurites are major constituents of senile plaques. Lab. Invest. 64: 826–832.PubMedGoogle Scholar
  23. Pettmann, B., and Henderson, C.E., 1998, Neuronal cell death. Neuron 20: 633–647.CrossRefPubMedGoogle Scholar
  24. Simon, J. P., and Aunis, D., 1989, Biochemistry of the chromogranin A protein family, Biochem. J. 262: 1–13.PubMedGoogle Scholar
  25. Strub, J.M., Goumon, Y., Lugardon, K., Capon, C., Lopez, M., Moniatte, M., Van Dorsselaer, A., Aunis, D., and Metz-Boutigue, M.H., 1996, Antibacterial activity of glycosylated and phosphorylated chromogranin A-derived peptide 173–194 from bovine adrenal medullary chromaffin granules. J. Biol. Chem. 271: 28533–28540.PubMedGoogle Scholar
  26. Taupenot, L., Ciesielski-Treska, J., Ulrich, G., Chasserot-Golaz, S., Aunis, D., and Bader, M.F., 1996, Chromogranin A triggers a phenotypic transformation and the generation of NO in brain microglial cells. Neuroscience 72: 377–389.CrossRefPubMedGoogle Scholar
  27. Winkler, H., and Fischer-Colbrie, R. (1992) The chromogranins A and B: the first 25 years and future perspectives. Neuroscience 49: 497–528.CrossRefPubMedGoogle Scholar
  28. Yasuhara, O., Kawamata, T., Aimi, Y., McGeer, E.G., and McGeer, P.L., 1994, Expression of chromogranin A in lesions in the central nervous system from patients with neurological diseases. Neurosci. Lett. 170: 13–16.CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Jaroslava Ciesielski-Treska
    • 1
  • Dominique Aunis
    • 1
  1. 1.Unité INSERM U-338 Biologie de la Communication CellulaireCentre de NeurochimieStrasbourgFrance

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