CHLORPYRIFOS INDUCES RETICULUM ENDOPLASMIC STRESS IN JEG-3 CELLS

REYNA, LUCIANA; RIDANO, MAGALI EVELIN; FLORES-MARTÍN, JESICA; PANZETTA-DUTARI, GRACIELA MARÍA; GENTI-RAIMONDI, SUSANA

Mar del Plata, Buenos Aires

Simposio; VI Latin American Symposium on Maternal-Fetal Interaction and Placenta and V Latin American Symposium on Reproductive Immunology Meeting 2015; 2015

Latin American Society for Maternal Fetal Interaction and Placenta

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. Particularly,we found that cells treated with 50 ìM or 100 ìM CPF lead to an early Nrf2 increase at both mRNA and protein levels, triggering the antioxidant status and nuclear Nrf2 translocation. Objectives: This work was performed to evaluate whether CPF induces reticulum endoplasmic (ER) stress in JEG-3 cells. Methods: Cells were exposed to 50 ìM or 100 ìM CPF for 3 or 24 h in conditions where cell viability was not altered. Western blot assays were used to explore the protein levels of ER stress biomarkers. Results: In response to CPF the ER stress biomarker proteins glucose regulated protein 78 and calnexin were significantly augmented at 24 h of treatment, whereas protein disulfide isomerase showed an increasing trend although statistically non-significant. Furthermore, CPF also activated inositol-requiring enzyme 1, a sensor for the unfolded protein response. Since reported studies indicate that p53 plays a critical role in the cellular response to ER stress, the effect of CPF was investigated by measuring p53 protein expression. The data indicate that CPF induces an early p53 expression at 3 h of CPF cell exposure which was recovered to the basal value at 24 h of CPF treatment. Conclusions: Altogether, these findings indicate that CPF induces ER stress in JEG-3 cells; however they are able to trigger an adaptive protection response against the xenobiotic injury. Supported by CONICET, FONCyT and SECyT-UNC