Evidence map›Paper›PMID 25349122›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2015

Identification of a functional antioxidant response element within the eighth intron of the human ABCC3 gene.

Mark J Canet, Matthew D Merrell, Bryan G Harder, Jonathan M Maher, Tongde Wu, Andrew J Lickteig, Jonathan P Jackson, Donna D Zhang, Masayuki Yamamoto, Nathan J Cherrington

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. ABCC3 Expressed by CD56International journal of molecular sciences · 2019
    Article
  7. Article
  8. Article
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  14. Review
  15. Review
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

10 authors at 2 institutions in 2 countries.

Mark J CanetDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (M.J.C., M.D.M., B.G.H. T.W., A.J.L., J.P.J., D.D.Z, N.J.C.); and Department of Medical Biochemistry, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan (J.M.M., M.Y.).
Matthew D MerrellDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (M.J.C., M.D.M., B.G.H. T.W., A.J.L., J.P.J., D.D.Z, N.J.C.); and Department of Medical Biochemistry, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan (J.M.M., M.Y.).
Bryan G HarderDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (M.J.C., M.D.M., B.G.H. T.W., A.J.L., J.P.J., D.D.Z, N.J.C.); and Department of Medical Biochemistry, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan (J.M.M., M.Y.).
Jonathan M MaherDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (M.J.C., M.D.M., B.G.H. T.W., A.J.L., J.P.J., D.D.Z, N.J.C.); and Department of Medical Biochemistry, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan (J.M.M., M.Y.).
Tongde WuDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (M.J.C., M.D.M., B.G.H. T.W., A.J.L., J.P.J., D.D.Z, N.J.C.); and Department of Medical Biochemistry, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan (J.M.M., M.Y.).
Andrew J LickteigDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (M.J.C., M.D.M., B.G.H. T.W., A.J.L., J.P.J., D.D.Z, N.J.C.); and Department of Medical Biochemistry, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan (J.M.M., M.Y.).
Jonathan P JacksonDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (M.J.C., M.D.M., B.G.H. T.W., A.J.L., J.P.J., D.D.Z, N.J.C.); and Department of Medical Biochemistry, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan (J.M.M., M.Y.).
Donna D ZhangDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (M.J.C., M.D.M., B.G.H. T.W., A.J.L., J.P.J., D.D.Z, N.J.C.); and Department of Medical Biochemistry, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan (J.M.M., M.Y.).
Masayuki YamamotoDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (M.J.C., M.D.M., B.G.H. T.W., A.J.L., J.P.J., D.D.Z, N.J.C.); and Department of Medical Biochemistry, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan (J.M.M., M.Y.).
Nathan J CherringtonDepartment of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (M.J.C., M.D.M., B.G.H. T.W., A.J.L., J.P.J., D.D.Z, N.J.C.); and Department of Medical Biochemistry, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan (J.M.M., M.Y.) cherrington@pharmacy.arizona.edu.
University of Arizona · USTohoku University · JP

Funding

SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI Paloma Inés Beamer · 1994 to 2026
$36.7M
Training in Environmental Toxicology of Human DiseaseT32ES007091 · NIEHS · UNIVERSITY OF ARIZONA · PI Nathan J Cherrington · 1985 to 2026
$10.7M
Pediatric Adverse Drug Reactions in NASHR01HD062489 · NICHD · UNIVERSITY OF ARIZONA · PI CHERRINGTON, NATHAN J · 2011 to 2015
$1.6M
Drug Transport at the Blood-Testis BarrierR01AI083927 · NIAID · UNIVERSITY OF ARIZONA · PI CHERRINGTON, NATHAN J · 2010 to 2013
$1.5M
NIAID NIH HHS AI083927NIAID NIH HHS R01 AI083927NICHD NIH HHS HD062489NICHD NIH HHS R01 HD062489NIEHS NIH HHS ES006694NIEHS NIH HHS ES007091NIEHS NIH HHS P30 ES006694NIEHS NIH HHS T32 ES007091
6 · The paper itself

Abstract

The ATP-binding cassette (ABC) family of transporters, including ABCC3, is a large family of efflux pumps that plays a pivotal role in the elimination of xenobiotics from the body. ABCC3 has been reported to be induced during hepatic stress conditions and through the progression of some forms of cancer. Several lines of evidence have implicated the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in this induction. However, although rodent models have been investigated, a functional antioxidant response element (ARE) in the human ABCC3 gene has not been identified. The purpose of this study was to identify and characterize the ARE(s) responsible for mediating the Nrf2-dependent induction of the human ABCC3 gene. A high-throughput chromatin immunoprecipitation-sequencing analysis performed in A549 cells revealed a specific interaction between Nrf2 and the eighth intron of the human ABCC3 gene rather than the more prototypical flanking region of the gene. Subsequent in silico analysis of the intron identified two putative ARE elements that contained the core consensus ARE sequence commonly found in several Nrf2-responsive genes. Functional characterization of these two AREs using luciferase-reporter constructs with ARE mutant constructs revealed that one of these putative AREs is functionally active. Finally, DNA pull-down assays confirmed specific binding of these intronic AREs by Nrf2 in vitro. Our findings identify a functional Nrf2 response element within the eighth intron of the ABCC3 gene, which may provide mechanistic insight into the induction of ABCC3 during antioxidant response stimuli.

Indexed as

Antioxidant Response ElementsAntioxidantsATP-Binding Cassette, Sub-Family C ProteinsCell Line, TumorHumansIntronsNF-E2-Related Factor 2Transcription FactorsAntioxidantsATP-Binding Cassette, Sub-Family C Proteinsmultidrug resistance-associated protein 3NF-E2-Related Factor 2Transcription Factors

Identifiers

PMID25349122
PMCPMC4279086
OpenAlexW2108220750

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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.