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Fibroblast Growth Factor 1 inhibits p53-dependent apoptosis in PC12 cells

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Abstract

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.

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Acknowledgements

This work was supported in part by grants from the “Association pour la Recherche Contre le Cancer” (#3367) and the “Ligue Nationale Contre le Cancer”. Sylvina Bouleau held successive fellowships from the “Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche” and the “Association pour la Recherche contre le Cancer”. Ioana Pârvu-Ferecatu is supported by a fellowships from the “Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche”.

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  1. 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

    Sylvina Bouleau, Ioana Pârvu-Ferecatu, Aida Rodriguez-Enfedaque, Vincent Rincheval, Hélène Grimal, Bernard Mignotte, Jean-Luc Vayssiere & Flore Renaud

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  1. Sylvina Bouleau
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Correspondence to Flore Renaud.

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Bouleau, S., Pârvu-Ferecatu, I., Rodriguez-Enfedaque, A. et al. Fibroblast Growth Factor 1 inhibits p53-dependent apoptosis in PC12 cells. Apoptosis 12, 1377–1387 (2007). https://doi.org/10.1007/s10495-007-0072-x

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