Fibroblast Growth Factor 1 inhibits p53-dependent apoptosis in PC12 cells.
The survival activity of FGF1 and the pro-apoptotic activity of p53 were characterized in vitro and/or in vivo for different types of neurons after different stresses and in different neurodegenerative pathologies. To investigate whether or not FGF1 and p53 pathways interact in neuronal cells, we studied the effect of FGF1 on p53-dependent apoptosis in PC12 cells. We first characterized p53-dependent PC12 cell death induced by etoposide (a DNA damaging agent). We showed that etoposide increased p53 stabilization, phosphorylation (Ser-15), nuclear translocation and transcriptional activity. In particular, p53 promoted mdm2, p21, puma and noxa expression in PC12 cells. The activation of p53 initiated a classical mitochondrial apoptosis process associated with caspases activation and nuclear degradation. We demonstrated that FGF1 protected PC12 cells from p53-dependent apoptosis upstream from mitochondrial and nuclear events. FGF1 inhibited etoposide-induced p53 phosphorylation, stabilization, nuclear translocation and transcriptional activity. This study presents the first evidence that FGF1 and p53 pathways interact in neuronal cells, and that FGF1 protects neuronal cells from p53-dependent apoptosis, suggesting that alterations of FGF1/p53 crosstalk could be involved in a large range of neurons and in neurological disorders.
Bouleau
Sylvina
S
Laboratoire de Génétique et Biologie Cellulaire, UMR 8159 CNRS, Université de Versailles/Saint Quentin-en Yvelines, Ecole Pratique des Hautes Etudes, 45 avenue des Etats-Unis, 78035, Versailles Cedex, France.
Pârvu-Ferecatu
Ioana
I
Rodriguez-Enfedaque
Aida
A
Rincheval
Vincent
V
Grimal
Hélène
H
Mignotte
Bernard
B
Vayssiere
Jean-Luc
JL
Renaud
Flore
F
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D059005:Topoisomerase II Inhibitors; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D059005:Topoisomerase II Inhibitors; D016159:Tumor Suppressor Protein p53; D016220:Fibroblast Growth Factor 1; D005047:Etoposide; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9