title: Bcl-xL inhibits different apoptotic pathways in rat PC12 cells.
abstract: Bcl-xL, a member of the bcl-2 family of proteins is required for the survival of neurons early in development. To study the mechanism of action of Bcl-xL in a neuronal context, we generated rat PC12 cells overexpressing Bcl-xL and examined their susceptibility to apoptotic stimuli that induce apoptosis through different pathways involving trophic-factor deprivation, staurosporine, tumor necrosis factor alpha or cisplatin. Overexpression of Bcl-xL in both naive and neuronal PC12 cells inhibited apoptosis induced by the different pathways. However, the extent of this protective effect varied, suggesting that the contribution of the Bcl-xL-controlled step to apoptosis differs in the different pathways. Our findings also showed that TNF alpha-induced activation of caspase-3 is inhibited by overexpression of Bcl-xL, suggesting that Bcl-xL acts upstream of caspase activation.
authors.affiliation: Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Lindenboim
authors.forename: R
authors.initials: R
authors.lastname: Haviv
authors.forename: R
authors.initials: R
authors.lastname: Stein
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology; D051020:bcl-X Protein
chemical_list: C494812:Bcl2l1 protein, mouse; C494813:Bcl2l1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D019311:Staurosporine; D002945:Cisplatin