Multiple pathways lead to activation of the survival mechanism in quiescent BALB/c-3T3 cells.
The survival of density-arrested quiescent murine BALB/c-3T3 cells in serum-free Dulbecco's medium requires the presence of cell growth factors or second messenger agonists. The protein synthesis inhibitor anisomycin blocks the survival-mediating action of the basic fibroblast growth factor (bFGF) and of 12-O-tetradecanoylphorbol 13-acetate (TPA), but has little or no effect on the protective action of platelet-derived growth factor or 8-bromoadenosine 3':5'-cyclic monophosphate (Br-cAMP). The effects of anisomycin are concentration dependent in the range from 2.5 to 25 microM and show that the survival-enhancing abilities of bFGF and TPA critically require protein synthesis, whereas those of platelet-derived growth factor and Br-cAMP do not. The survival-mediating action of bFGF and TPA can also be blocked with the RNA synthesis inhibitors actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), whereas the action of platelet-derived growth factor and Br-cAMP is largely resistant. Results on the time course of action of DRB, a selective inhibitor of the synthesis of mRNA precursor molecules, suggest that the RNA required for the survival-enhancing action of bFGF and TPA is present in cells at the time of serum withdrawal and addition of the survival factor and has a half-life greater than 3 h. The new evidence provides further support for the hypothesis that protection of serum-deprived, density-arrested BALB/c-3T3 fibroblasts against death can be achieved either via pathways that entail the synthesis of protein and RNA (e.g., via diacylglycerol-protein kinase C) or via pathways that do not involve de novo biosynthesis (e.g., via cAMP-protein kinase A).
Tamm
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Cell Physiology and Virology Laboratory, Rockefeller University, New York, New York 10021.
Kikuchi
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D016475:3T3 Cells; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D016895:Culture Media, Serum-Free; D003609:Dactinomycin / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D016895:Culture Media, Serum-Free; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2; D003609:Dactinomycin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000841:Anisomycin; D013755:Tetradecanoylphorbol Acetate