Bax and Bak proteins require caspase activity to trigger apoptosis in sympathetic neurons.
We show that the pro-apoptotic proteins Bax and Bak trigger apoptosis when over-expressed in sympathetic neurons cultured in the presence of NGF. This effect can be blocked with z-VAD-fmk, a peptide inhibitor of caspases, but not with anti-apoptotic chemical compounds such as antioxidants or proteasome inhibitors. These results demonstrate that in sympathetic neurons Bax and Bak are sufficient to induce apoptosis in the absence of any other apparent cell death stimulus and that their effect is mediated by caspases but does not require reactive oxygen species nor activity of the proteasome.
Martinou
I
I
Geneva Biomedical Research Institute, Plan-Les-Ouates, Glaxo-Wellcome, Switzerland.
Missotten
M
M
Fernandez
P A
PA
Sadoul
R
R
Martinou
J C
JC
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D008565:Membrane Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D051381:Rats; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000502:physiology*; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
D000590:Amino Acid Chloromethyl Ketones; C494774:Bak1 protein, rat; C494828:Bax protein, rat; D015853:Cysteine Proteinase Inhibitors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010726:Phosphodiesterase Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C067713:lactacystin; D003546:Cysteine Endopeptidases; D003676:Deferoxamine; D000111:Acetylcysteine