Advertisement

Neuronal Differentiation of PC12 Cells in the Absence of Extracellular Matrix Adhesion Induces Apoptosis

  • Herbert W. Harris
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)

Abstract

In recent years, evidence has accumulated implicating programmed cell death as a major mechanism underlying neurodegenerative processes. Programmed cell death has been described in a wide range of cell types in response to diverse factors including steroids, cytokines, ionizing radiation, virus infection, and many other agents1. It is an active process that is often dependent on RNA and protein synthesis and probably involves a number of complex pathways that ultimately result in endonuclease activation, DNA fragmentation, and cell death. Programmed cell death may be distinguished form “accidental” cell death that results from hypoxia, trauma, or toxic agents, although all of these processes may involve common pathways2. In the brain, programmed cell death has been well established as a part of normal development3, following excitotoxic death of targets of innervation4, and as a consequence of amyloid toxicity5,6. These findings suggest that programmed cell death may be a central common pathway in numerous neurodenegerative processes including Alzheimer’s disease. This concept is supported by observations that neurons are strictly dependent on growth factors to prevent programmed cell death and promote survival7 and by evidence that growth factor response mechanisms are attenuated in aging8.

Keywords

PC12 Cell Nerve Growth Factor Programme Cell Death Focal Adhesion Kinase Matrix Adhesion 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    L. Fesus, Biochemical Events in Naturally Occurring Forms of Cell Death. FEBS. 328:1 (1993).CrossRefGoogle Scholar
  2. 2.
    R.A. Schwartzman and J.A. Cidlowski, Apoptosis: the biochemistry and molecular biology of programmed cell death. Endocr Rev. 14:133 (1993).PubMedGoogle Scholar
  3. 3.
    K.A. Wood, B. Dipasquale, and R.J. Youle, In situ labeling of granule cells for apoptosis-associated DNA fragmentation reveals different mechanisms of cell loss in developing cerebellum. Neuron. 11:621 (1993).PubMedCrossRefGoogle Scholar
  4. 4.
    A. Macaya, F. Munell, R.M. Gubits, and R.E. Burke, Apoptosis in substantia nigra following developmental striatal excitotoxic injury. Proc Natl Acad Sci USA. 91: 8117 (1994).PubMedCrossRefGoogle Scholar
  5. 5.
    D.T. Loo, A. Copani, C.J. Pike, E.R. Whittemore A.J. Walencewicz and C.W. Cotman, Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. Proc Natl Acad Sci USA. 90: 7951 (1993).PubMedCrossRefGoogle Scholar
  6. 6.
    G. Forloni, Beta-Amyloid neurotoxicity. Funct Neurol. 8: 211 (1993).PubMedGoogle Scholar
  7. 7.
    M.C. Raff, B.A. Barres, J.F. Burne, H.S. Coles, Y. Ishizaki, and M.D. Jacobson, Programmed cell death and the control of cell survival: lessons from the nervous system, Science. 262: 695 (1993).PubMedCrossRefGoogle Scholar
  8. 8.
    L. Olson, NGF and the treatment of Alzheimer’s disease, Exp Neurol. 124: 5 (1993).PubMedCrossRefGoogle Scholar
  9. 9.
    E. Ruoslahti, and J.C. Reed, Anchorage dependence, integrins, and apoptosis, Cell. 77: 477 (1994).PubMedCrossRefGoogle Scholar
  10. 10.
    J.J. Meredith, B. Fazeli, and M.A. Schwartz, M.A. Schwertz The extracellular matrix as a cell survival factor, Mol Biol Cell. 4: 953 (1993).PubMedGoogle Scholar
  11. 11.
    F. Re, A. Zanetti, M. Sironi, N. Polentarutti, L. Lanfrancone, E. Dejana, and F. Colotta, Inhibition of anchorage-dependent cell spreading triggers apoptosis in cultured human endothelial cells, J Cell Biol. 127: 537 (1994).PubMedCrossRefGoogle Scholar
  12. 12.
    S.M. Frisch, and H. Francis, Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 124: 619 (1994).PubMedCrossRefGoogle Scholar
  13. 13.
    N. Boudreau, C.J. Sympson, Z. Werb, and MJ. Bissell, Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Science. 267: 891 (1995).PubMedCrossRefGoogle Scholar
  14. 14.
    IT. Parsons, M.D. Schaller, J. Hildebrand, T.H. Leu, A. Richardson, and C. Otey, Focal adhesion kinase: structure and signalling. J Cell Sci Suppl, 18:109 (1994).PubMedCrossRefGoogle Scholar
  15. 15.
    E.A. Clark, and J.S. Brugge, Integrins and signal transduction pathways: the road taken, Science. 268: 233 (1995).PubMedCrossRefGoogle Scholar
  16. 16.
    Q. Chen, M.S. Kinch, T.S. Lin, K. Burridge, and L. Juliano, Integrin-mediated cell. adhesion activates mitogen-activated kinases. J. Biol. Chem. 269: 26602 (1994).PubMedGoogle Scholar
  17. 17.
    E. Ruoslahti, Y Yamaguchi, A. Hildebrand, and W.A. Border, Extracellular matrix/growth factor interactions, Cold Spring Harbor Symp. Quant.Biol. 57:309 (1992).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Herbert W. Harris
    • 1
  1. 1.Laboratory of NeurosciencesNational Institute on Aging, National Institutes of HealthBethesdaUSA

Personalised recommendations