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 parathio...

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Published in:Environmental toxicology 2017-02, Vol.32 (2), p.490-500
Main Authors: Medina‐Díaz, Irma Martha, Ponce‐Ruiz, Néstor, Ramírez‐Chávez, Bryana, Rojas‐García, Aurora Elizabeth, Barrón‐Vivanco, Briscia S., Elizondo, Guillermo, Bernal‐Hernández, Yael Y.
Format: Article
Language:English
Subjects:
Aryldialkylphosphatase - genetics
Aryldialkylphosphatase - metabolism
Cell Survival - drug effects
Chlorpyrifos - toxicity
Cytokines - genetics
Cytokines - metabolism
Down-Regulation - drug effects
gene expression
Hep G2 Cells
Human Hepatocellular Carcinoma (HepG2)
Humans
Insecticides - toxicity
Methyl Parathion - toxicity
Organophosphorus Compounds - toxicity
organophosphorus pesticides
Oxidative Stress - drug effects
Paraoxonase 1
Real-Time Polymerase Chain Reaction
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Summary: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.
ISSN:1520-4081
1522-7278
DOI:10.1002/tox.22253