title: Downregulation of human paraoxonase 1 (PON1) by organophosphate pesticides in HepG2 cells.
abstract: Paraoxonase 1 (PON1) is a calcium-dependent esterase synthesized primarily in the liver and secreted into the plasma where it is associated with high-density lipoproteins (HDL). PON1 hydrolyzes and detoxifies some toxic metabolites of organophosphorus compounds (OPs) such as methyl parathion and chlorpyrifos. Thus, PON1 activity and expression levels are important for determining susceptibility against OPs poisoning. Some studies have demonstrated that OPs can modulate gene expression through interactions with nuclear receptors. In this study, we evaluated the effects of methyl parathion and chlorpyrifos on the modulation of PON1 in Human Hepatocellular Carcinoma (HepG2) cells by real-time PCR, PON1 activity assay, and western blot. The results showed that the treatments with methyl parathion and chlorpyrifos decreased PON1 mRNA and immunoreactive protein and increased inflammatory cytokines in HepG2 cells. The effects of methyl parathion and chlorpyrifos on the downregulation of PON1 gene expression in HepG2 cells may provide evidence of OPs cytotoxicity related to oxidative stress and an inflammatory response. A decrease in the expression of the PON1 gene may increase the susceptibility to OPs intoxication and the risk of diseases related to inflammation and oxidative stress. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 490-500, 2017.
authors.affiliation: Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado.
authors.forename: Irma Martha
authors.initials: IM
authors.lastname: Medina-Díaz
authors.affiliation: Posgrado en Ciencias Biológico Agropecuarias, Universidad Autónoma de Nayarit.
authors.forename: Néstor
authors.initials: N
authors.lastname: Ponce-Ruiz
authors.affiliation: Posgrado en Ciencias Biológico Agropecuarias, Universidad Autónoma de Nayarit.
authors.forename: Bryana
authors.initials: B
authors.lastname: Ramírez-Chávez
authors.affiliation: Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado.
authors.forename: Aurora Elizabeth
authors.initials: AE
authors.lastname: Rojas-García
authors.affiliation: Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado.
authors.forename: Briscia S
authors.initials: BS
authors.lastname: Barrón-Vivanco
authors.affiliation: Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, México, D.F., México.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Elizondo
authors.affiliation: Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado.
authors.forename: Yael Y
authors.initials: YY
authors.lastname: Bernal-Hernández
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D008743:Methyl Parathion / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D007306:Insecticides; D009943:Organophosphorus Compounds; D008743:Methyl Parathion; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D004390:Chlorpyrifos
keywords: Human Hepatocellular Carcinoma (HepG2); Paraoxonase 1; gene expression; organophosphorus pesticides