The neuroprotective effect of talipexole from paraquat-induced cell death in dopaminergic neuronal cells.

Rubén Gómez-Sánchez, José M Bravo-San Pedro, Mireia Niso-Santano, Germán Soler, José M Fuentes, Rosa A González-Polo, Rubén Gómez-Sánchez, José M. Bravo-San Pedro, Mireia Niso-Santano, Germán Soler, José M. Fuentes, Rosa A. González-Polo

Index: Neurotoxicology 31(6) , 701-8, (2010)

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Abstract

Talipexole is a non-ergot dopamine (DA) agonist that has been used in the treatment of Parkinson's disease. In the present study, we examined the effect of talipexole on paraquat (PQ)-induced N27 cell death and the intracellular pathways involved in this effect. Pretreatment of N27 cells with talipexole (1mM) resulted in significant protection against paraquat-induced cell death. In N27 cells, talipexole inhibited paraquat-induced apoptotic hallmarks such as cytochrome c release, caspase-3 activation, chromatin condensation and externalization of phosphatidilserine. Talipexole pretreatment prevents the reduction in the anti-apoptotic Bcl-x(L) protein and increases in the pro-apoptotic form of Bak and p-Bad, both induced by PQ. Finally, we also observed that talipexole abrogates the activation of cell death pathways JNK1/2 and p38 produced by PQ, and increases the phosphorylated (active) forms of the pro-survival pathways ERK1/2 and Akt. These results reveal that talipexole exerts a neuroprotective effect in a mesencephalic cell line exposed to the neurotoxin PQ, which is related to the etiology of Parkinson's disease.Copyright © 2010 Elsevier Inc. All rights reserved.