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Neurotoxicity Induced by Okadaic Acid in the Human Neuroblastoma SH-SY5Y Line Can Be Differentially Prevented by alpha 7 and beta 2*Nicotinic Stimulation


Reference:

del Barrio, L., Martin-de-Saavedra, M. D., Romero, A., Parada, E., Egea, J., Avila, J., McIntosh, J. M., Wonnacott, S. and Lopez, M. G., 2011. Neurotoxicity Induced by Okadaic Acid in the Human Neuroblastoma SH-SY5Y Line Can Be Differentially Prevented by alpha 7 and beta 2*Nicotinic Stimulation. Toxicological Sciences, 123 (1), pp. 193-205.

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    Official URL:

    http://dx.doi.org/10.1093/toxsci/kfr163

    Abstract

    A good model of neuronal death that reproduces the characteristic tau (tau) hyperphosphorylation of Alzheimers disease is the use of okadaic acid (OA). The aim of this study was to determine the contribution of alpha 7 and beta 2* nicotinic acetylcholine receptor (nAChR) subtypes to neuroprotection against OA in the SH-SY5Y cell line by using the selective alpha 7 and beta 2* nAChR agonists PNU 282987 and 5-Iodo-A85380, respectively. The results of this study show that both alpha 7 and beta 2* nAChR can afford neuroprotection against OA-induced neurotoxicity. Protection mediated by alpha 7 nAChRs was independent of Ca(2+) and involved the intracellular signaling pathway Janus Kinase-2/Phosphatidylinositol-3-kinase/Akt. When Ca(2+) entry was promoted through the alpha 7 nAChR by using the alpha 7-selective positive allosteric modulator PNU 120596, protection was lost. By contrast, protection mediated by beta 2* nAChRs was Ca(2+) dependent and implicated the signaling pathways PI3K/Akt and extracellular regulated kinase 1/2. Both alpha 7 and beta 2* nAChR activation converged on downregulation of GSK-3 beta and reduction of tau phosphorylation in cells undergoing cell death induced by OA. Therefore, targeting nAChR could offer a strategy for reducing neurodegeneration secondary to hyperphosphorylation of protein tau.

    Details

    Item Type Articles
    Creatorsdel Barrio, L., Martin-de-Saavedra, M. D., Romero, A., Parada, E., Egea, J., Avila, J., McIntosh, J. M., Wonnacott, S. and Lopez, M. G.
    DOI10.1093/toxsci/kfr163
    Uncontrolled Keywords5ia 85380, sh-sy5y neuroblastoma, pnu 282987, nicotinic receptors, okadaic acid, hyperphosphorylation of tau
    DepartmentsFaculty of Science > Biology & Biochemistry
    Publisher StatementWonnacott_Tox-Sci_2011_123_1_193.pdf: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Toxicological Sciences following peer review. The definitive publisher-authenticated version del Barrio, L., Martin-de-Saavedra, M. D., Romero, A., Parada, E., Egea, J., Avila, J., McIntosh, J. M., Wonnacott, S. and Lopez, M. G., 2011. Neurotoxicity Induced by Okadaic Acid in the Human Neuroblastoma SH-SY5Y Line Can Be Differentially Prevented by alpha 7 and beta 2*Nicotinic Stimulation. Toxicological Sciences, 123 (1), pp. 193-205 is available online at: http://dx.doi.org/10.1093/toxsci/kfr163
    RefereedYes
    StatusPublished
    ID Code26146

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