PMID- 29524743
OWN - NLM
STAT- MEDLINE
DCOM- 20180605
LR  - 20240329
IS  - 1879-1514 (Electronic)
IS  - 0166-445X (Print)
IS  - 0166-445X (Linking)
VI  - 198
DP  - 2018 May
TI  - Nrf2a modulates the embryonic antioxidant response to perfluorooctanesulfonic 
      acid (PFOS) in the zebrafish, Danio rerio.
PG  - 92-102
LID - S0166-445X(18)30134-6 [pii]
LID - 10.1016/j.aquatox.2018.02.010 [doi]
AB  - 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 nrf2a(fh318-/-) mutant embryos were exposed 
      daily to 0 (0.01% v/v DMSO), 16, 32, or 64 muM 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.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Sant, Karilyn E
AU  - Sant KE
AD  - Department of Environmental Health Sciences, School of Public Health and Health 
      Sciences, University of Massachusetts, Amherst, MA 01003, United States.
FAU - Sinno, Paul P
AU  - Sinno PP
AD  - Department of Environmental Health Sciences, School of Public Health and Health 
      Sciences, University of Massachusetts, Amherst, MA 01003, United States.
FAU - Jacobs, Haydee M
AU  - Jacobs HM
AD  - Department of Environmental Health Sciences, School of Public Health and Health 
      Sciences, University of Massachusetts, Amherst, MA 01003, United States.
FAU - Timme-Laragy, Alicia R
AU  - Timme-Laragy AR
AD  - Department of Environmental Health Sciences, School of Public Health and Health 
      Sciences, University of Massachusetts, Amherst, MA 01003, United States. 
      Electronic address: aliciat@umass.edu.
LA  - eng
GR  - F32 ES028085/ES/NIEHS NIH HHS/United States
GR  - R01 ES025748/ES/NIEHS NIH HHS/United States
GR  - R01 ES028201/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20180220
PL  - Netherlands
TA  - Aquat Toxicol
JT  - Aquatic toxicology (Amsterdam, Netherlands)
JID - 8500246
RN  - 0 (Alkanesulfonic Acids)
RN  - 0 (Antioxidants)
RN  - K848JZ4886 (Cysteine)
RN  - 0 (Fluorocarbons)
RN  - GAN16C9B8O (Glutathione)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (nfe2l2a protein, zebrafish)
RN  - 9H2MAI21CL (perfluorooctane sulfonic acid)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factors)
RN  - 0 (Water Pollutants, Chemical)
RN  - 0 (Zebrafish Proteins)
SB  - IM
MH  - Animals
MH  - *Alkanesulfonic Acids/toxicity
MH  - *Antioxidants/metabolism
MH  - Apoptosis/drug effects/genetics
MH  - Binding Sites
MH  - Cysteine/metabolism
MH  - *Embryo, Nonmammalian/drug effects/metabolism
MH  - Embryonic Development/drug effects
MH  - *Fluorocarbons/toxicity
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Glutathione/metabolism
MH  - NF-E2-Related Factor 2
MH  - Oxidation-Reduction
MH  - Oxidative Stress/drug effects
MH  - Peroxisome Proliferator-Activated Receptors/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - Transcription Factors/metabolism
MH  - Water Pollutants, Chemical/toxicity
MH  - *Zebrafish/embryology/genetics
MH  - *Zebrafish Proteins/metabolism
PMC - PMC6077977
MID - NIHMS950551
OTO - NOTNLM
OT  - Embryo
OT  - Glutathione
OT  - Nfe2l2
OT  - PFAS
OT  - Perfluorinated
OT  - Redox
EDAT- 2018/03/11 06:00
MHDA- 2018/06/05 06:00
PMCR- 2019/05/01
CRDT- 2018/03/11 06:00
PHST- 2017/08/22 00:00 [received]
PHST- 2018/02/12 00:00 [revised]
PHST- 2018/02/13 00:00 [accepted]
PHST- 2018/03/11 06:00 [pubmed]
PHST- 2018/06/05 06:00 [medline]
PHST- 2018/03/11 06:00 [entrez]
PHST- 2019/05/01 00:00 [pmc-release]
AID - S0166-445X(18)30134-6 [pii]
AID - 10.1016/j.aquatox.2018.02.010 [doi]
PST - ppublish
SO  - Aquat Toxicol. 2018 May;198:92-102. doi: 10.1016/j.aquatox.2018.02.010. Epub 2018 
      Feb 20.