Evidence map›Paper›PMID 23726801›Full record

ArticleToxicology and applied pharmacology2013

The cytochrome P450 2AA gene cluster in zebrafish (Danio rerio): expression of CYP2AA1 and CYP2AA2 and response to phenobarbital-type inducers.

Akira Kubota, Afonso C D Bainy, Bruce R Woodin, Jared V Goldstone, John J Stegeman

Open access · greenAbstract read
In one paragraph

Article in Toxicology and applied pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
7.0field-weighted citation impact, top 3% 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

16 citing papers in PubMed, 34 citations in OpenAlex.

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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

5 authors at 2 institutions in 2 countries.

Akira KubotaBiology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
Afonso C D Bainy
Bruce R Woodin
Jared V Goldstone
John J Stegeman
Woods Hole Oceanographic Institution · USUniversidade Federal de Santa Catarina · BR

Funding

Training CoreP42ES007381 · NIEHS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SHERR, DAVID H · 1995 to 2019
$46.1M
CYP Genes and the Generation of Oxidative StressR01ES015912 · NIEHS · WOODS HOLE OCEANOGRAPHIC INSTITUTION · PI STEGEMAN, JOHN J · 2007 to 2011
$3.1M
Nomenclature of Human and Vertebrate GenesU41HG003345 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI BIRNEY, EWAN, BRUFORD, ELSPETH · 2013 to 2017
$2.4M
NHGRI NIH HHS U41 HG003345NIEHS NIH HHS 5P42ES007381NIEHS NIH HHS P42 ES007381NIEHS NIH HHS R01 ES015912NIEHS NIH HHS R01ES015912
6 · The paper itself

Abstract

The cytochrome P450 (CYP) 2 gene family is the largest and most diverse CYP gene family in vertebrates. In zebrafish, we have identified 10 genes in a new subfamily, CYP2AA, which does not show orthology to any human or other mammalian CYP genes. Here we report evolutionary and structural relationships of the 10 CYP2AA genes and expression of the first two genes, CYP2AA1 and CYP2AA2. Parsimony reconstruction of the tandem duplication pattern for the CYP2AA cluster suggests that CYP2AA1, CYP2AA2 and CYP2AA3 likely arose in the earlier duplication events and thus are most diverged in function from the other CYP2AAs. On the other hand, CYP2AA8 and CYP2AA9 are genes that arose in the latest duplication event, implying functional similarity between these two CYPs. A molecular model of CYP2AA1 showing the sequence conservation across the CYP2AA cluster reveals that the regions with the highest variability within the cluster map onto CYP2AA1 near the substrate access channels, suggesting differing substrate specificities. Zebrafish CYP2AA1 transcript was expressed predominantly in the intestine, while CYP2AA2 was most highly expressed in the kidney, suggesting differing roles in physiology. In the liver CYP2AA2 expression but not that of CYP2AA1, was increased by 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) and, to a lesser extent, by phenobarbital (PB). In contrast, pregnenolone 16α-carbonitrile (PCN) increased CYP2AA1 expression, but not CYP2AA2 in the liver. The results identify a CYP2 subfamily in zebrafish that includes genes apparently induced by PB-type chemicals and PXR agonists, the first concrete in vivo evidence for a PB-type response in fish.

Indexed as

AnimalsBiological EvolutionCloning, MolecularCytochrome P-450 Enzyme SystemEnzyme InductionFemaleGene Expression Regulation, EnzymologicMaleModels, MolecularOrgan SpecificityPhenobarbitalPregnenolone CarbonitrilePyridinesReal-Time Polymerase Chain ReactionRNA, MessengerXenobiotics1,4-bis(2-(3,5-dichloropyridyloxy))benzeneCYP2AA1 protein, zebrafishCYP2AA2 protein, zebrafishCytochrome P-450 Enzyme SystemPhenobarbitalPregnenolone CarbonitrilePyridinesRNA, MessengerXenobioticsZebrafish ProteinsCYP2Cytochrome P450Homology modelingMolecular evolutionPhenobarbitalZebrafish

Identifiers

PMID23726801
PMCPMC3846545
OpenAlexW2035673046

What OpenQuestion holds

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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.