title: Chlorpyrifos induces endoplasmic reticulum stress in JEG-3 cells.
abstract: 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 50μM or 100μM CPF during 24h 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 GRP78/BiP and IRE1α, a sensor for the unfolded protein response, as well as in phospho-eIF2α and XBP1 mRNA splicing. Additionally, CPF led to a decrease in p53 protein expression. The downregulation of p53 levels induced by CPF was partially blocked when cells were exposed to CPF in the presence of the proteasome inhibitor MG132. Altogether, these findings point out that CPF induces ER stress in JEG-3 cells; however these cells are able to attenuate it downregulating the levels of the pro-apoptotic protein p53.
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología, X5000HUA Córdoba, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Reyna
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología, X5000HUA Córdoba, Argentina.
authors.forename: Jésica
authors.initials: J
authors.lastname: Flores-Martín
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología, X5000HUA Córdoba, Argentina.
authors.forename: Magali E
authors.initials: ME
authors.lastname: Ridano
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología, X5000HUA Córdoba, Argentina.
authors.forename: Graciela M
authors.initials: GM
authors.lastname: Panzetta-Dutari
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología, X5000HUA Córdoba, Argentina. Electronic address: sgenti@fcq.unc.edu.ar.
authors.forename: Susana
authors.initials: S
authors.lastname: Genti-Raimondi
mesh_terms: D045744:Cell Line, Tumor; D004390:Chlorpyrifos / Q000633:toxicity*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000071717:X-Box Binding Protein 1 / Q000235:genetics
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D007306:Insecticides; D016159:Tumor Suppressor Protein p53; D000071717:X-Box Binding Protein 1; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; D004390:Chlorpyrifos
keywords: Chlorpyrifos; Endoplasmic reticulum stress; JEG-3 cells; p53