Evaluation of pathways involved in pentachlorophenol-induced apoptosis in rat neurons

Folch, Jaume; Yeste-Velasco, Marc; Alvira, Daniel; Vazquez de la Torre, Aureli; Bordas, Meritxell; Lopez, Marta; Sureda, Francesc X.; Rimbau, Victor; Camins, Antoni; Pallas, Merce


Pentachlorophenol (PCP) (C6HCl5O) is a synthetic toxic organochloride fungicide for humans which exhibit neurotoxic properties. In the present research, we describe the potential pathways implicated in PCP-induced apoptosis in an acute model of toxicity in rat cerebellar granule neurons (CGNs). In our experiments, acute exposure of CGNs to micromolar concentrations of PCP induced the transcriptional activity of genes related to the classical apoptosis pathway (caspase 3, caspase 8, Bad), oxidative stress and glutathione metabolism (glutathione peroxidase-1, catalase, glutathione-S-transferase-3 and superoxide dismutase-1), and mitogenic response (cyclin D1, cdk2, cdk4, cdkn2b). Results from Western blot also shown significative increases in the expression of cyclins D1, E and A and cdk4. The mitogenic response was also related to a significative increase in the phosphorylation of retinoblastoma protein (Rb). PCP would cause apoptosis up-regulating the transcriptional. activity of p53 gene and also increasing their activation by phosphorylation, concomitant with a decrease in the sirtuin 1 content. In conclusion, acute exposure of CGNs to PCP induces the classical p53 apoptotic pathway, promotes the up-regulation of several genes related to oxidative stress and the over-expression of molecules involved in the cell cycle control. (C) 2009 Elsevier Inc. All rights reserved.

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Título según WOS: ID WOS:000266279200016 Not found in local WOS DB
Título de la Revista: Neurotoxicology
Volumen: 30
Número: 3
Fecha de publicación: 2009
Página de inicio: 451
Página final: 458


Notas: ISI