Adenovirus-Mediated Transfer of Bcl-X L Protects Neuronal Cells from Bax-Induced Apoptosis

Adenovirus-Mediated Transfer of Bcl-X L Protects Neuronal Cells from Bax-Induced Apoptosis Bax-mediated apoptosis in neurons is involved in many pathologic conditions affecting the central nervous system, including degenerative diseases, stroke, and trauma. Two molecules belonging to the Bcl-2 family, Bcl-2 and Bcl-X L , protect cells from Bax-induced apoptosis and show distinct expression patterns in adult neurons, with downregulated Bcl-2 and highly upregulated Bcl-X L expression. To investigate the biological functions of these two molecules in Bax-mediated apoptosis in neurons, we transduced various levels of Bcl-X L or Bcl-2 via adenoviral vectors into nerve growth factor (NGF)-treated PC12 cells. Overexpression of Bax induced drastic apoptosis in NGF-treated PC12 cells. Bcl-X L expressed at a wide range of levels conferred a high level of protection against Bax-mediated apoptosis. In contrast, Bcl-2 at various levels conferred far less protection against apoptosis. Moreover, Bcl-X L protected PC12 cells from apoptosis induced by NGF withdrawal. These data indicate that Bcl-X L -mediated protection is the major pathway that suppresses apoptosis in NGF-treated PC12 cells and that Bcl-X L would be a more relevant target of manipulation in future treatment strategies, including gene therapies. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Cell Research Elsevier

Adenovirus-Mediated Transfer of Bcl-X L Protects Neuronal Cells from Bax-Induced Apoptosis

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Publisher
Elsevier
Copyright
Copyright © 2000 Academic Press
ISSN
0014-4827
D.O.I.
10.1006/excr.1999.4751
Publisher site
See Article on Publisher Site

Abstract

Bax-mediated apoptosis in neurons is involved in many pathologic conditions affecting the central nervous system, including degenerative diseases, stroke, and trauma. Two molecules belonging to the Bcl-2 family, Bcl-2 and Bcl-X L , protect cells from Bax-induced apoptosis and show distinct expression patterns in adult neurons, with downregulated Bcl-2 and highly upregulated Bcl-X L expression. To investigate the biological functions of these two molecules in Bax-mediated apoptosis in neurons, we transduced various levels of Bcl-X L or Bcl-2 via adenoviral vectors into nerve growth factor (NGF)-treated PC12 cells. Overexpression of Bax induced drastic apoptosis in NGF-treated PC12 cells. Bcl-X L expressed at a wide range of levels conferred a high level of protection against Bax-mediated apoptosis. In contrast, Bcl-2 at various levels conferred far less protection against apoptosis. Moreover, Bcl-X L protected PC12 cells from apoptosis induced by NGF withdrawal. These data indicate that Bcl-X L -mediated protection is the major pathway that suppresses apoptosis in NGF-treated PC12 cells and that Bcl-X L would be a more relevant target of manipulation in future treatment strategies, including gene therapies.

Journal

Experimental Cell ResearchElsevier

Published: Feb 1, 2000

References

  • Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons
    Slack, R.S.; Belliveau, D.J.; Rosenberg, M.; Atwal, J.; Lochmuller, H.; Aloyz, R.; Haghighi, A.; Lach, B.; Seth, P.; Cooper, E.; Miller, F.D.
  • Viral proteins E1B19K and p35 protect sympathetic neurons from cell death induced by NGF deprivation
    Martinou, I.; Fernandez, P.A.; Missotten, M.; White, E.; Allet, B.; Sadoul, R.; Martinou, J.C.
  • Bax expression in mammalian neurons undergoing apoptosis, and in Alzheimer's disease hippocampus
    Macgibbon, G.A.; Lawlor, P.A.; Sirimanne, E.S.; Walton, M.R.; Connor, B.; Young, D.; Williams, C.; Gluckman, P.; Faull, R.L.; Hughes, P.; Dragunow, M.
  • p53 and Bax activation in 6-hydroxydopamine-induced apoptosis in PC12 cells
    Blum, D.; Wu, Y.; Nissou, M.F.; Arnaud, S.; Alim-Louis-Benabid; Verna, J.M.
  • Altered expression of Bcl-2 and Bax mRNA in amyotrophic lateral sclerosis spinal cord motor neurons
    Mu, X.; He, J.; Anderson, D.W.; Trojanowski, J.Q.; Springer, J.E.
  • Expression pattern of candidate cell death effector proteins Bax, Bcl-2, Bcl-X, and c-Jun in sensory and motor neurons following sciatic nerve transection in the rat
    Gillardon, F.; Klimaschewski, L.; Wickert, H.; Krajewski, S.; Reed, J.C.; Zimmermann, M.
  • Adenovirus-mediated inducible gene expression through tetracycline-controllable transactivator with nuclear localization signal
    Yoshida, Y.; Hamada, H.
  • Overexpression of HA-Bax but not Bcl-2 or Bcl-X L attenuates 6-hydroxydopamine-induced neuronal apoptosis
    Oh, J.H.; Choi, W.S.; Kim, J.E.; Seo, J.W.; O'Malley, K.L.; Oh, Y.J.
  • Developmental patterns of BCL-2 and BCL-X polypeptide expression in the human spinal cord
    Yachnis, A.T.; Giovanini, M.A.; Eskin, T.A.; Reier, P.J.; Anderson, D.K.

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