The neuroprotective effect of talipexole from paraquat-induced cell death in dopaminergic neuronal cells.
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.
Gómez-Sánchez
Rubén
R
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Departamento de Bioquímica y Biología Molecular y Genética, EU Enfermería y TO, Universidad de Extremadura, Avda Universidad s/n, Cáceres, Spain.
Bravo-San Pedro
José M
JM
Niso-Santano
Mireia
M
Soler
Germán
G
Fuentes
José M
JM
González-Polo
Rosa A
RA
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010269:Paraquat / Q000633:toxicity*; D051381:Rats
D001381:Azepines; D018491:Dopamine Agonists; D018696:Neuroprotective Agents; C024763:talipexole; D010269:Paraquat; D004298:Dopamine