Inhibition of protein kinase C protects against paraoxon-mediated neuronal cell death.
Neurotoxicology
; 28(4): 843-9, 2007 Jul.
Article
en En
| MEDLINE
| ID: mdl-17561261
Paraoxon, the active metabolite of parathion, is an acetylcholinesterases (AChE) inhibitor that kills cultured cerebellar granule cell neurons via an apoptotic mechanism. Protein kinase C is an enzyme with diverse functions but its role in paraoxon-induced cell death is unknown. We show that a neurotoxic concentration of paraoxon increases PKC phosphorylation. We tested whether PKC is involved in paraoxon-induced neuronal cell death by using the PKC activator, phorbol 12-myristate 13-acetate (TPA). TPA increases PKC activity and enhances the neurotoxic effect of paraoxon by 28%. In sharp contrast, addition of the PKC inhibitor Ro-31-8220 protects more than 30% neurons that would otherwise die from paraoxon-induced neuronal cell death in either a pretreatment or post-treatment paradigm and markedly reduces phospho-PKC pan levels. We also show that the pretreatment of Ro-31-8220 blocks paraoxon-induced caspase-3 activity completely. These results suggest that activation of protein kinase C is required for paraoxon neurotoxicity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Paraoxon
/
Proteína Quinasa C
/
Regulación de la Expresión Génica
/
Inhibidores de la Colinesterasa
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Neurotoxicology
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Países Bajos