title: IGF-I protects cortical neurons against ceramide-induced apoptosis via activation of the PI-3K/Akt and ERK pathways; is this protection independent of CREB and Bcl-2?
abstract: Current understanding of IGF-I-mediated neuroprotection implies the activation of phosphatidylinositol-3-kinase (PI-3K), which leads to the activation of Akt/Protein Kinase B. In non-neuronal cells, Akt phosphorylates and activates the transcription factor CREB, implicated in the transcription of the anti-apoptotic bcl-2 gene. This paper further analyses the anti-apoptotic IGF-I action in neurons. We show that IGF-I protects cortical neurons against ceramide-induced apoptosis. Ceramide decreases Akt phosphorylation during apoptotic process whereas a simultaneous treatment with IGF-I increases Akt phosphorylation. Analysis of the signal transduction pathways revealed that IGF-I induces CREB phosphorylation via PI-3K and ERK, whereas simultaneous ceramide and IGF-I treatment decreases CREB phosphorylation. Although an overexpression of Bcl-2 protects cortical neurons against ceramide-induced apoptosis, our data indicate that the Bcl-2 protein level is not modulated during IGF-I, ceramide and/or LY294002 treatment. In consequence, we demonstrated that IGF protects neurons against ceramide-induced apoptosis and that IGF-I protection involves the PI-3K/Akt and ERK pathways; this protection may be independent of CREB and Bcl-2.
authors.affiliation: Laboratoire Neurobiologie des Processus Adaptatifs (UMR 7102 CNRS and Univ. P. and M. Curie), 9 quai Saint Bernard, 75005 Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Willaime-Morawek
authors.forename: Nicolas
authors.initials: N
authors.lastname: Arbez
authors.forename: Jean
authors.initials: J
authors.lastname: Mariani
authors.forename: Bernard
authors.initials: B
authors.lastname: Brugg
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002518:Ceramides / Q000633:toxicity; D002540:Cerebral Cortex / Q000166:cytology*; D002867:Chromones / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019254:Genes, bcl-2 / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D007150:Immunohistochemistry / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: D002518:Ceramides; D002867:Chromones; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D009025:Morpholines; D049452:Green Fluorescent Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases