Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/57925
Título : Neurotoxicity Induced by Okadaic Acid in the Human Neuroblastoma SH-SY5Y Line Can Be Differentially Prevented by α7 and β2* Nicotinic Stimulation
Autor : del Barrio, Laura, Martín-de-Saavedra, María Dolores, Romero, Alejandro, Parada, Esther, Egea, Javier, Avila, Jesús, McIntosh, John Michael, Wonnacott, Susan, López, Manuela G.
Palabras clave : Okadaic acid
SH-SY5Y neuroblastoma
Nicotinic receptors
Hyperphosphorylation of tau
PNU 282987
5IA 85380
Fecha de publicación : 2011
Editor: Oxford University Press
Citación : Toxicological Sciences 123 (1): 193-205 (2011)
Resumen: A good model of neuronal death that reproduces the characteristic tau (τ) hyperphosphorylation of Alzheimeŕs disease is the use of okadaic acid (OA). The aim of this study was to determine the contribution of α7 and β2* nicotinic acetylcholine receptor (nAChR) subtypes to neuroprotection against OA in the SH-SY5Y cell line by using the selective α7 and β2* nAChR agonists PNU 282987 and 5-Iodo-A85380, respectively. The results of this study show that both α7 and β2* nAChR can afford neuroprotection against OA-induced neurotoxicity. Protection mediated by α7 nAChRs was independent of Ca2+ and involved the intracellular signaling pathway Janus Kinase-2/Phosphatidylinositol-3-kinase/Akt. When Ca2+ entry was promoted through the α7 nAChR by using the α7-selective positive allosteric modulator PNU 120596, protection was lost. By contrast, protection mediated by β2* nAChRs was Ca2+ dependent and implicated the signaling pathways PI3K/Akt and extracellular regulated kinase 1/2. Both α7 and β2* nAChR activation converged on downregulation of GSK-3β and reduction of τ phosphorylation in cells undergoing cell death induced by OA. Therefore, targeting nAChR could offer a strategy for reducing neurodegeneration secondary to hyperphosphorylation of protein τ.
Versión del editor: http://dx.doi.org/10.1093/toxsci/kfr163
URI : http://hdl.handle.net/10261/57925
ISSN: 1096-6080
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