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Glia-conditioned medium induces de novo synthesis of tyrosine hydroxylase and increases dopamine cell survival by differential signaling pathways

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons84751

Canals,  S
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Zitation

de Bernardo, S., Canals, S., Casarejos MJ, Rodríguez-Martín, E., & Mena, M. (2003). Glia-conditioned medium induces de novo synthesis of tyrosine hydroxylase and increases dopamine cell survival by differential signaling pathways. Journal of Neuroscience Research, 73(6), 818-830. doi:10.1002/jnr.10704.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0013-DBA3-B
Zusammenfassung
The mesencephalic astroglia-conditioned medium (GCM) greatly increases dopamine (DA) phenotype expression, and it also protects from spontaneous and toxin-induced cell death in midbrain cultures. In this study, we have investigated the signaling pathways implicated in those effects. Genistein at 5 M, an inhibitor of tyrosine kinase receptors, and KT-5720, a protein kinase A inhibitor, blocked the GCM-induced effects on DA phenotype expression and DA cell survival but did not abolish the increased astrocytic (glial fibrillary acidic protein-positive; GFAP+) processes. We analyzed the role of phosphatidylinositol-3 kinase (PI-3K) on TH induction and cell survival, with the PI-3K inhibitors LY-294002 and wortmannin, and the role of the phosphorylation of mitogen-activated protein kinase (MAPK) with PD-98059, a p-ERK1/2 MAPK inhibitor. LY-294002 at 20-30 M blocked the GCM-induced effects on TH expression and DA cell survival but did not abolish the increased astrocytic processes. PD-98059 at 20 and 40 M blocked the GCM-induced effects on DA phenotype, cell survival, and GFAP expression. However, staurosporine at 10 nM, a protein kinase C inhibitor, only blocked the protective effects induced by GCM on midbrain cell apoptosis. The data presented herein show that tyrosine kinase receptors, cAMP-dependent protein kinase, PI-3K, and MAPK signaling pathways are implicated in de novo synthesis of TH+ cells induced by GCM as well as in DA cell apoptosis and that these effects are unrelated to increased GFAP expression. PKC inhibitors only abolished the GCM-induced effects on midbrain neuronal survival, suggesting that signaling pathways for DA phenotype expression and survival may be independent.