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

Authors
Journal
NeuroToxicology
0161-813X
Publisher
Elsevier
Publication Date
Volume
31
Issue
6
Identifiers
DOI: 10.1016/j.neuro.2010.07.005
Keywords
  • Talipexole
  • Parkinson'S Disease
  • Paraquat
  • Apoptosis
  • Neuroprotection
Disciplines
  • Biology
  • Medicine

Abstract

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 (1 mM) 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.

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