Adenovirus-mediated transfer of Bcl-X(L) protects neuronal cells from Bax-induced apoptosis

Exp Cell Res. 2000 Feb 1;254(2):221-31. doi: 10.1006/excr.1999.4751.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Gene Expression Regulation
  • Genetic Vectors
  • Kinetics
  • Nerve Growth Factors / pharmacology
  • Neurons / cytology
  • Neurons / physiology
  • PC12 Cells
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats
  • Recombinant Proteins / metabolism
  • Transfection / methods
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • beta-Galactosidase / genetics

Substances

  • Bax protein, rat
  • Bcl2l1 protein, rat
  • Nerve Growth Factors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • beta-Galactosidase