Epigenetic modulation of Nrf2 and Ogg1 gene expression in testicular germ cells by methyl parathion exposure
AffiliationUniv Arizona, Coll Pharm, Dept Pharmacol & Toxicol
MetadataShow full item record
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
CitationD. Hernandez-Cortes, I. Alvarado-Cruz, M.J. Solís-Heredia, B. Quintanilla-Vega, Epigenetic modulation of Nrf2 and Ogg1 gene expression in testicular germ cells by methyl parathion exposure, Toxicology and Applied Pharmacology, 346, pp 19-27, https://doi.org/10.1016/j.taap.2018.03.010
Rights© 2018 Published by Elsevier Inc.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractMethyl parathion (Me-Pa) is an oxidizing organophosphate (OP) pesticide that generates reactive oxygen species (ROS) through its biotransformation. Some studies have also suggested that OP pesticides have the capacity to alkylate biomolecules, including DNA. In general, DNA methylation in gene promoters represses transcription. NRF2 is a key transcription factor that regulates the expression of antioxidant, metabolic and detoxifying genes through the antioxidant response element (ARE) situated in promoters of regulated genes. Furthermore, DNA repair genes, including 8-oxoguanine DNA glycosidase (OGG1), have been proposed as NRF2 target genes. Me-Pa exposure produces poor semen quality, genetic and oxidative damage in sperm cells, and reduced fertility. However, the Me-Pa effects on the methylation status and the expression of antioxidant (Nrf2) or DNA repair (Ogg1) genes in male germ cells have not been investigated. Therefore, mice were exposed to Me-Pa to evaluate the global (%5-mC) and specific methylation of Nrf2 and 0:4:1 genes using pyrosequencing, gene expression, and total protein carbonylation in male germ cells. The results showed that Me-Pa significantly decreased the global DNA methylation pattern and significantly increased the methylation of two CpG sites within Ogg1 promoter and one CpG site within Nrf2 promoter, In addition, Ogg1 or Nrf2 expression did not change after Me-Pa exposure despite the oxidative damage produced. Altogether, our data suggest that Me-Pa toxicity alters Ogg1 and Nrf2 promoter methylation in male germ cells that may be modulating their gene expression.
Note12 month embargo; published online: 11 March 2018
VersionFinal accepted manuscript
SponsorsCONACYT (National Council of Science and Technology)-Mexico
- Prenatal exposure to metals modified DNA methylation and the expression of antioxidant- and DNA defense-related genes in newborns in an urban area.
- Authors: Montes-Castro N, Alvarado-Cruz I, Torres-Sánchez L, García-Aguiar I, Barrera-Hernández A, Escamilla-Núñez C, Del Razo LM, Quintanilla-Vega B
- Issue date: 2019 Sep
- Effect of Arsenic Exposure on NRF2-KEAP1 Pathway and Epigenetic Modification.
- Authors: Janasik B, Reszka E, Stanislawska M, Jablonska E, Kuras R, Wieczorek E, Malachowska B, Fendler W, Wasowicz W
- Issue date: 2018 Sep
- A γ-tocopherol-rich mixture of tocopherols maintains Nrf2 expression in prostate tumors of TRAMP mice via epigenetic inhibition of CpG methylation.
- Authors: Huang Y, Khor TO, Shu L, Saw CL, Wu TY, Suh N, Yang CS, Kong AN
- Issue date: 2012 May
- Novel protective mechanism of reducing renal cell damage in diabetes: Activation AMPK by AICAR increased NRF2/OGG1 proteins and reduced oxidative DNA damage.
- Authors: Habib SL, Yadav A, Kidane D, Weiss RH, Liang S
- Issue date: 2016 Nov 16
- Triphlorethol-A from Ecklonia cava up-regulates the oxidant sensitive 8-oxoguanine DNA glycosylase 1.
- Authors: Kim KC, Lee IK, Kang KA, Piao MJ, Ryu MJ, Kim JM, Lee NH, Hyun JW
- Issue date: 2014 Oct 28