PUBLICATION

The Role of Nrf2 and MAPK Pathways in PFOS-induced Oxidative Stress in Zebrafish Embryos

Authors
Shi, X., and Zhou, B.
ID
ZDB-PUB-100309-15
Date
2010
Source
Toxicological sciences : an official journal of the Society of Toxicology   115(2): 391-400 (Journal)
Registered Authors
Keywords
PFOS, ROS, Oxidative stress, Nrf2, MAPKs, Zebrafish
MeSH Terms
  • Alkanesulfonic Acids/toxicity*
  • Animals
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian/drug effects*
  • Embryo, Nonmammalian/metabolism
  • Fluorocarbons/toxicity*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental/drug effects
  • Heme Oxygenase-1/genetics
  • Heme Oxygenase-1/metabolism
  • Isothiocyanates
  • MAP Kinase Signaling System/drug effects*
  • MAP Kinase Signaling System/genetics
  • Malondialdehyde/metabolism
  • Mitogen-Activated Protein Kinases/genetics
  • Mitogen-Activated Protein Kinases/metabolism*
  • NF-E2-Related Factor 2/antagonists & inhibitors
  • NF-E2-Related Factor 2/genetics
  • NF-E2-Related Factor 2/metabolism*
  • Oxidative Stress/drug effects*
  • Reactive Oxygen Species/metabolism
  • Thiocyanates/pharmacology
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
20200220 Full text @ Toxicol. Sci.
CTD
20200220
Abstract
Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant and causes oxidative stress, apoptosis and developmental toxicity in zebrafish embryos. In the present study, we examined nuclear factor erythroid 2-related factors 2 (Nrf2) and mitogen-activated protein kinases (MAPKs) mediated oxidative stress pathways in zebrafish embryos upon exposure to PFOS. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to 0.2, 0.4 and 1.0 mg/L PFOS until 96 hpf. PFOS enhanced production of reactive oxygen species (ROS) in a concentration-dependent manner. Activity of antioxidative enzymes, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were significantly induced in zebrafish larvae in all PFOS-treated groups relative to the control. Exposure to 1.0 mg/L PFOS significantly increased malondialdehyde (MDA) production in zebrafish larvae. The Nrf2 and heme oxygenase-1 (HO-1) gene expressions were both significantly up-regulated compared with the control group. For MAPKs, we investigated gene expression profiles of extracellular signal-regulated protein kinase (ERK), c-Jun NH (2)-terminal kinase (JNK) and p38. The ERK gene expression levels were unchanged, whereas JNK and p38 gene expressions were significantly up-regulated, which could be linked to PFOS-induced cell apoptosis in zebrafish larvae. In addition, we found that co-exposure with sulforaphane (SFN), an Nrf2 activator, could significantly protect against PFOS-induced ROS generation, while inhibition of MAPKs did not exhibit significant effects on PFOS-induced HO-1 gene expression and ROS production. Furthermore, we showed that morpholino-mediated knockdown of Nrf2 reduced PFOS-induced HO-1 gene expression. These findings demonstrate that Nrf2 is protective against PFOS-induced oxidative stress in zebrafish larvae.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping