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
Citation
Shi, X., and Zhou, B. (2010) The Role of Nrf2 and MAPK Pathways in PFOS-induced Oxidative Stress in Zebrafish Embryos. Toxicological sciences : an official journal of the Society of Toxicology. 115(2):391-400.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping