PACAP and C2-ceramide generate different AP-1 complexes through a MAP-kinase-dependent pathway: involvement of c-Fos in PACAP-induced Bcl-2 expression
| Autor: | Cecile Fisch, Xavier Xifró, Jean‐François Lebigot, Nicolas Aubert, Bruno J. Gonzalez, Alain Fournier, Hubert Vaudry, Stephane De Jouffrey, José Rodríguez-Alvarez, David Vaudry, Anthony Falluel-Morel |
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| Přispěvatelé: | Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIT (CIT), CIT, Laboratory of Biochemistry and Molecular Biology, Neuroscience Institute-Autonomous University of Barcelona, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), This work was supported by INSERM (U413), the CIT, a France-Quebec exchange program (INSERM-FRSQ), the Regional Platform for Cell Imaging, and the Conseil Régional de Haute-Normandie |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Proto-Oncogene Proteins c-jun
MESH: Neurons Apoptosis Biochemistry c-Fos MESH: Animals Newborn MESH: Down-Regulation MESH: Dose-Response Relationship Drug 0302 clinical medicine Sphingosine Gene expression Phosphoprotein Phosphatases MESH: Animals Protein Phosphatase 2 Enzyme Inhibitors Phosphorylation Cells Cultured Neurons 0303 health sciences Kinase MESH: Proto-Oncogene Proteins c-fos MESH: Protein Phosphatase 2 MESH: Gene Expression Regulation MESH: Transcription Factor AP-1 3. Good health DNA-Binding Proteins Proto-Oncogene Proteins c-bcl-2 MESH: Cell Survival MESH: Enzyme Inhibitors Mitogen-activated protein kinase [SDV.TOX]Life Sciences [q-bio]/Toxicology Pituitary Adenylate Cyclase-Activating Polypeptide MESH: Sphingosine Proto-Oncogene Proteins c-fos hormones hormone substitutes and hormone antagonists MESH: Cells Cultured Transcriptional Activation endocrine system MESH: Rats Cell Survival MAP Kinase Signaling System Down-Regulation Adenylate kinase Biology Cerebellar Cortex 03 medical and health sciences Cellular and Molecular Neuroscience MESH: Phosphoprotein Phosphatases Animals Rats Wistar Protein kinase A 030304 developmental biology MESH: Cerebellar Cortex Dose-Response Relationship Drug MESH: Phosphorylation MESH: Proto-Oncogene Proteins c-jun MESH: MAP Kinase Signaling System MESH: Apoptosis MESH: Pituitary Adenylate Cyclase-Activating Polypeptide Protein phosphatase 2 MESH: Rats Wistar Molecular biology Rats Transcription Factor AP-1 Animals Newborn Gene Expression Regulation MESH: Proto-Oncogene Proteins c-bcl-2 biology.protein MESH: Transcriptional Activation 030217 neurology & neurosurgery MESH: DNA-Binding Proteins |
| Zdroj: | Journal of Neurochemistry Journal of Neurochemistry, Wiley, 2006, 99 (4), pp.1237-50. ⟨10.1111/j.1471-4159.2006.04148.x⟩ |
| ISSN: | 0022-3042 1471-4159 |
| Popis: | International audience; The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) inhibits C2-ceramide-induced cell death through blockade of the mitochondrial apoptotic pathway in rat cerebellar granule neurones. However, the gene induction processes and transcription factors involved in the anti-apoptotic effect of PACAP remain unknown. Here, we show that PACAP and C2-ceramide activate activator protein-1 (AP-1) DNA binding in a dose- and time-dependent manner, but generate different AP-1 dimers. Thus, PACAP increased the proportion of c-Fos and Jun D while C2-ceramide increased c-Jun and reduced c-Fos in AP-1 complexes. In addition, PACAP strongly activated c-Fos gene expression while C2-ceramide markedly increased c-Jun phosphorylation. The effect of PACAP on c-Fos expression was blocked by the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitor, U0126, while phosphorylation of c-Jun induced by C2-ceramide was abrogated by the protein phosphatase 2A (PP2A) inhibitor, okadaic acid. Transfection of immature granule cells with c-Fos siRNA, which strongly reduced basal and PACAP-stimulated levels of the protein, totally prevented the stimulatory effect of PACAP on Bcl-2 expression. The present study demonstrates that AP-1 complexes containing c-Fos mediate the effect of PACAP on Bcl-2 gene expression in cerebellar granule neurones. Our data also indicate that different AP-1 dimers are associated with the pro-apoptotic effect of C2-ceramide and the anti-apoptotic effect of PACAP. |
| Databáze: | OpenAIRE |
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