Bcl-2 protects from oxidative damage and apoptotic cell death without interfering with activation of NF-kappa B by TNF.
The recent demonstration of the anti-oxidant properties of the Bcl-2 gene product suggested that expression of Bcl-2 may interfere with the nuclear migration of the NF-kappa B transcription factor, which is thought to depend on the presence of reactive oxygen intermediates. In mouse L cells, overexpression of Bcl-2 interfered with the activation of NF-kappa B by H2O2. However, Bcl-2 had no effect on the activation of NF-kappa B by TNF, even though it protected cells from TNF-induced apoptosis. The effects of exogenous pyrrolidine dithiocarbamate were very similar to those of Bcl-2 overexpression. We conclude that the protective effects of anti-oxidants against induced apoptotic cell death are unrelated to their ability to interfere with NF-kappa B activation.
Albrecht
H
H
Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
Tschopp
J
J
Jongeneel
C V
CV
D000818:Animals; D000975:Antioxidants; D017209:Apoptosis; D001483:Base Sequence; D002460:Cell Line; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000975:Antioxidants; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases