Differential regulation of AKT, MAPK and GSK3? during C2-ceramide-induced neuronal death
Evidence has implicated apoptosis as a mechanism underlying cell demise in diverse neurodegenerative diseases including Parkinson's disease (PD). Endogenous toxins and other stress signals activate the sphingomyelin pathway increasing the levels of ceramide, an important regulator of cell death...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2010 |
| País: | Colombia |
| Institución: | Universidad del Rosario |
| Repositorio: | Repositorio EdocUR - U. Rosario |
| Idioma: | inglés |
| OAI Identifier: | oai:repository.urosario.edu.co:10336/22659 |
| Acceso en línea: | https://doi.org/10.1016/j.neuro.2010.08.001 https://repository.urosario.edu.co/handle/10336/22659 |
| Access Level: | acceso abierto |
| Palabra clave: | Ceramide Glycogen synthase kinase 3beta Mitogen activated protein kinase Neurotrophin 3 Protein kinase b Somatomedin c Article Cell culture Cell line Cell survival Controlled study Drug exposure Enzyme activation Enzyme inhibition Enzyme phosphorylation Enzyme regulation Nerve cell necrosis Neuroprotection Priority journal Animals Cell death Glycogen synthase kinase 3 Insulin-like growth factor i Mice Mitogen-activated protein kinases Neurons Neuroprotective agents Proto-oncogene proteins c-akt Sphingosine Akt Apoptosis Cad cells Gsk3? Igf-1 Mapk |
| Sumario: | Evidence has implicated apoptosis as a mechanism underlying cell demise in diverse neurodegenerative diseases including Parkinson's disease (PD). Endogenous toxins and other stress signals activate the sphingomyelin pathway increasing the levels of ceramide, an important regulator of cell death.In the present paper we have analysed the contribution of PI3K/AKT-GSK3? and MAPK (ERK and JNK) pathways to cell death in a catecholaminergic cell line following exposure to C2-ceramide. We also explored the potential neuroprotective action of insulin-like growth factor-1 (IGF-1) and neurotrophin-3 (NT3).We demonstrated that C2-ceramide-induced cell death is associated to an early decrease in phosphorylation (inhibition) of PI3K/AKT and ERK, followed by phosphorylation (activation) of JNK and de-phosphorylation (activation) of glycogen synthase kinase-3 beta (GSK3?). NT3 and IGF-1 increased survival at early time points, but only IGF-1 is capable to attenuate C2-ceramide-mediated neuronal death, and this neuroprotection is associated to strong and permanent activation of AKT and inhibition of GSK3?. In conclusion, C2-ceramide initiates a series of events including an early inactivation of PI3K/AKT and ERK pathways followed by activation of JNK and activation of GSK3? and neuronal death, changes that are counteracted by IGF-1. © 2010 Elsevier Inc. |
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