Chlorpyrifos induces Endoplasmic Reticulum Stress associated with p53 degradation in JEG-3 cells

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

Córdoba

Congreso; LII Reunión Anual. Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2016

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

Chlorpyrifos (CPF) is an organophosphorous pesticide widely used in agricultural, industrial, and household applications.We have previously shown that JEG-3 cells are able to attenuate the oxidative stress induced by CPF through the adaptive activation of the Nrf2/ARE pathway. Considering that there is a relationship between oxidative stress and endoplasmic reticulum stress (ER), herein we investigated whether CPF also induces ER stress in JEG-3 cells. Cells were exposed to 50 μM or 100 μM CPF during 24 h in conditions where cell viability was not altered. Western blot and PCR assays were used to explore the protein and mRNA levels of ER stress biomarkers, respectively. CPF induced an increase of the typical ER stress-related proteins, such as BiP/78 kDa glucose-regulated protein and inositol-requiring enzyme 1α, a sensor for the unfolded protein response, as well as the phosphorylation of eIF-2α and XBP1 splicing. Additionally, CPF led to a decrease in p53 protein expression. The downregulation of p53 protein levels was blocked when cells were exposed to CPF in the presence of the proteasome inhibitor MG132 indicating that the p53 half-life was decreased by ER stress. Altogether, these findings point out that CPF induces ER stress in JEG-3 cells; however are able to attenuate it by downregulation of the pro-apoptotic p53 protein levels.Supported by CONICET, FONCyT and SECyT-UNC.