Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Nrf2a modulates the embryonic antioxidant response to perfluorooctanesulfonic acid (PFOS) in the zebrafish, Danio rerio.

Authors: Sant, Karilyn E; Sinno, Paul P; Jacobs, Haydee M; Timme-Laragy, Alicia R

Published In Aquat Toxicol, (2018 May)

Abstract: The glutathione redox system undergoes precise and dynamic changes during embryonic development, protecting against and mitigating oxidative insults. The antioxidant response is coordinately largely by the transcription factor Nuclear factor erythroid-2 (Nrf2), an endogenous sensor for cellular oxidative stress. We have previously demonstrated that impaired Nrf family signaling disrupts the glutathione redox system in the zebrafish embryo, and that impaired Nrf2 function increases embryonic sensitivity to environmental toxicants. Here, we investigated the persistent environmental toxicant and reported pro-oxidant perfluorooctanesulfonic acid (PFOS), and its impact on the embryonic glutathione-mediated redox environment. We further examined whether impaired Nrf2a function exacerbates PFOS-induced oxidative stress and embryotoxicity in the zebrafish, and the potential for Nrf2-PPAR crosstalk in the embryonic adaptive response. Wild-type and nrf2afh318-/- mutant embryos were exposed daily to 0 (0.01% v/v DMSO), 16, 32, or 64 μM PFOS beginning at 3 h post fertilization (hpf). Embryonic glutathione and cysteine redox environments were examined at 72 hpf. Gross embryonic toxicity, antioxidant gene expression, and apoptosis were examined at 96 hpf. Mortality, pericardial edema, and yolk sac utilization were increased in wild-type embryos exposed to PFOS. Embryonic glutathione and cysteine redox couples and gene expression of Nrf2 pathway targets were modulated by both exposure and genotype. Apoptosis was increased in PFOS-exposed wild-type embryos, though not in nrf2a mutants. In silico examination of putative transcription factor binding site suggested potential crosstalk between Nrf2 and PPAR signaling, since expression of PPARs and gene targets was modulated by both PFOS exposure and Nrf2a genotype. Overall, this work demonstrates that nrf2a modulates the embryonic response to PFOS, and that PPAR signaling may play a role in the embryonic adaptive response to PFOS.

PubMed ID: 29524743 Exiting the NIEHS site

MeSH Terms: Alkanesulfonic Acids*/toxicity; Animals; Antioxidants*/metabolism; Apoptosis/drug effects; Apoptosis/genetics; Binding Sites; Cysteine/metabolism; Embryo, Nonmammalian*/drug effects; Embryo, Nonmammalian*/metabolism; Embryonic Development/drug effects; Fluorocarbons*/toxicity; Gene Expression Regulation, Developmental/drug effects; Glutathione/metabolism; NF-E2-Related Factor 2; Oxidation-Reduction; Oxidative Stress/drug effects; Peroxisome Proliferator-Activated Receptors/genetics; Peroxisome Proliferator-Activated Receptors/metabolism; Reactive Oxygen Species/metabolism; Signal Transduction/drug effects; Transcription Factors/metabolism; Water Pollutants, Chemical/toxicity; Zebrafish Proteins*/metabolism; Zebrafish*/embryology; Zebrafish*/genetics

Back
to Top