Evidence map›Paper›PMID 26325326›Full record

ArticleAquatic toxicology (Amsterdam, Netherlands)2015

Regulation of Ahr signaling by Nrf2 during development: Effects of Nrf2a deficiency on PCB126 embryotoxicity in zebrafish (Danio rerio).

Michelle E Rousseau, Karilyn E Sant, Linnea R Borden, Diana G Franks, Mark E Hahn, Alicia R Timme-Laragy

Open access · greenAbstract read
In one paragraph

Article in Aquatic toxicology (Amsterdam, Netherlands), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 56 citations in OpenAlex.

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  16. A Review of the Functional Roles of the Zebrafish Aryl Hydrocarbon Receptors.Toxicological sciences : an official journal of the Society of Toxicology · 2020
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Michelle E RousseauDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United States. Electronic address: merousse@umass.edu.
Karilyn E SantDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United States. Electronic address: ksant@umass.edu.
Linnea R BordenDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United States. Electronic address: lborden@umass.edu.
Diana G FranksBiology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, United States. Electronic address: dfranks@whoi.edu.
Mark E HahnBiology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, United States. Electronic address: mhahn@whoi.edu.
Alicia R Timme-LaragyDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United States; Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, United States. Electronic address: aliciat@umass.edu.
University of Massachusetts Amherst · USWoods Hole Oceanographic Institution · US

Funding

AHR Signaling in Mammalian and Non-Mammalian ModelsR01ES006272 · NIEHS · WOODS HOLE OCEANOGRAPHIC INSTITUTION · PI HAHN, MARK E · 1999 to 2014
$4.1M
Mechanisms of Embryo Response to Oxidative StressR01ES016366 · NIEHS · WOODS HOLE OCEANOGRAPHIC INSTITUTION · PI HAHN, MARK E · 2009 to 2013
$1.9M
Differential Sensitivity to Oxidative Stress during Embryonic DevelopmentF32ES017585 · NIEHS · WOODS HOLE OCEANOGRAPHIC INSTITUTION · PI TIMME-LARAGY, ALICIA R · 2009 to 2011
$154k
NIEHS NIH HHS F32 ES017585NIEHS NIH HHS F32ES017585NIEHS NIH HHS R01 ES006272NIEHS NIH HHS R01ES006272NIEHS NIH HHS R01 ES016366NIEHS NIH HHS R01ES016366
6 · The paper itself

Abstract

The embryotoxicity of co-planar PCBs is regulated by the aryl hydrocarbon receptor (Ahr), and has been reported to involve oxidative stress. Ahr participates in crosstalk with another transcription factor, Nfe2l2, or Nrf2. Nrf2 binds to antioxidant response elements to regulate the adaptive response to oxidative stress. To explore aspects of the crosstalk between Nrf2 and Ahr and its impact on development, we used zebrafish (Danio rerio) with a mutated DNA binding domain in Nrf2a (nrf2a(fh318/fh318)), rendering these embryos more sensitive to oxidative stress. Embryos were exposed to 2 nM or 5 nM PCB126 at 24 h post fertilization (prim-5 stage of pharyngula) and examined for gene expression and morphology at 4 days post fertilization (dpf; protruding - mouth stage). Nrf2a mutant eleutheroembryos were more sensitive to PCB126 toxicity at 4 dpf, and in the absence of treatment also displayed some subtle developmental differences from wildtype embryos, including delayed inflation of the swim bladder and smaller yolk sacs. We used qPCR to measure changes in expression of the nrf gene family, keap1a, keap1b, the ahr gene family, and known target genes. cyp1a induction by PCB126 was enhanced in the Nrf2a mutants (156-fold in wildtypes vs. 228-fold in mutants exposed to 5 nM). Decreased expression of heme oxygenase (decycling) 1 (hmox1) in the Nrf2a mutants was accompanied by increased nrf2b expression. Target genes of Nrf2a and AhR2, NAD(P)H:quinone oxidoreductase 1 (nqo1) and glutathione S-transferase, alpha-like (gsta1), showed a 2-5-fold increase in expression in the Nrf2a mutants as compared to wildtype. This study elucidates the interaction between two important transcription factor pathways in the developmental toxicity of co-planar PCBs.

Indexed as

AnimalsEmbryo, NonmammalianGene Expression Regulation, DevelopmentalNF-E2-Related Factor 2Oxidative StressPolychlorinated BiphenylsReceptors, Aryl HydrocarbonSignal TransductionWater Pollutants, ChemicalZebrafishZebrafish Proteins3,4,5,3',4'-pentachlorobiphenylnfe2l2a protein, zebrafishNF-E2-Related Factor 2Polychlorinated BiphenylsReceptors, Aryl HydrocarbonWater Pollutants, ChemicalZebrafish ProteinsDioxin-like compoundEmbryonic developmentGene expressionSwim bladderTranscription factorYolk

Identifiers

PMID26325326
PMCPMC4703126
OpenAlexW1845508194

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.