Assessment of mechanisms involved in trophoblast response of Chlorpyrifos (CPF) Pesticide exposure

RIDANO, M.E; RACCA A; FLORES MARTIN J; REYNA L; GENTI RAIMONDI S; PANZETTA DUTARI G

Rosario, Santa Fe

Congreso; L Reunión Anual. Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2014

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Prior studies have shown that CPF induces ROS production in trophoblastic cells; however, they are quite resistant to cytotoxicity. In this context, JEG3 cells increase ABCG2 xenobiotic transporter and βhCG expression, and trigger anantioxidant response with augmented Nrf2 expression and nuclear translocation. KLF6 is an early response factor enriched in placenta, involved in βhCG transcription and upregulated by ROS. Here, we addressed whether thesetranscription factors mediate CPF effects on JEG3 cells. KLF6 protein level increased in cells exposed to CPF for 3h, preceding βhCG and ABCG2 activation observed after 24h of treatment. When KLF6-silenced cells were treated with50 µM CPF for 24 and 48h, cell viability was not affected; whereas βhCG and ABCG2 transcript and protein levels, measured by real time PCR and western-blot respectively, were increased to similar levels than in non-silenced cells.Compared to controls, Nrf2-silenced cells presented lower ABCG2 level but its expression as well as βhCG remained inducible by CPF. In summary, CPF increase Nrf2 and KLF6 levels though they are not the main factors mediatingCPF-induced upregulation of ABCG2 and βhCG in trophoblast cells. We are investigating if the AhR, involved in xenobiotic toxicity and recently described as a novel KLF6 partner, participates in JEG3 cell response to CPF.Supported by CONICET, FONCyT & SECyT-UNC.