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Research ArticleArticle

Expression and Localization of Rat Aldo-Keto Reductases and Induction of the 1B13 and 1D2 Isoforms by Phenolic Antioxidants

A. Kenneth MacLeod, Vincent P. Kelly, Larry G. Higgins, Michael O. Kelleher, Sally A. Price, Alison L. Bigley, Graham R. Betton and John D. Hayes
Drug Metabolism and Disposition February 2010, 38 (2) 341-346; DOI: https://doi.org/10.1124/dmd.109.030544
A. Kenneth MacLeod
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Vincent P. Kelly
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Larry G. Higgins
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Michael O. Kelleher
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Sally A. Price
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Alison L. Bigley
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Graham R. Betton
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John D. Hayes
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Abstract

The aldo-keto reductase (AKR) phase I drug metabolism enzyme superfamily is implicated in detoxification or bioactivation of a wide variety of carbonyl-bearing compounds. In this study, we have used antibodies raised against purified recombinant rat AKR isoforms 1A3, 1B4, 1C9, 1D2, and 7A1 to characterize the expression profile of these superfamily members in the rat and define their localization by immunohistochemistry. Western blotting showed that AKR1A3, AKR1B4, and AKR1C9 are ubiquitously expressed, whereas AKR1D2 and AKR7A1 are present in liver, adrenal gland, and kidney, with the latter also present in testis, spleen, and stomach. Immunohistochemical analysis of the kidney demonstrated the localization of AKR1A3 in proximal convoluted tubules, AKR1B4 in the loop of Henle, and AKR1C9 in the pars recta S3 segment of proximal tubules. We also report localization of AKR1B4 in the adrenal gland (parenchymal cells of the zona reticularis) and testis (Sertoli cells and late spermatids), of AKR1D2 in the liver (hepatocyte nuclei), and of AKR7A1 in the pancreatic duct and bronchiolar epithelium. Previous studies have shown that expression of AKR7A1 is induced in response to dietary administration of the phenolic antioxidants butylated hydroxyanisole and ethoxyquin. Here we identify AKR1B13 and AKR1D2 as further inducible members of the rat AKR superfamily.

Footnotes

  • This work was supported in part by Cancer Research-UK [Grant C4909/A7161]; and the Association for International Cancer Research [Grant 05-154].

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    10.1124/dmd.109.030544.

  • AKR
    aldo-keto reductase
    BHA
    butylated hydroxyanisole
    EQ
    ethoxyquin
    NQO1
    NAD(P)H:quinone oxidoreductase 1
    RT
    real-time
    PCR
    polymerase chain reaction
    TBST
    Tris-buffered saline Tween
    IHC
    immunohistochemical
    LoH
    loop of Henle
    NRF2
    nuclear factor-erythroid 2-related factor 2
    BA
    bile acid
    FXR
    farnesoid X receptor
    TGR5
    transmembrane G protein-coupled receptor 5
    GSTP1
    glutathione S-transferase Pi 1
    ARE
    antioxidant response element
    kb
    kilobase(s).

    • Received September 29, 2009.
    • Accepted November 13, 2009.
  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 38 (2)
Drug Metabolism and Disposition
Vol. 38, Issue 2
1 Feb 2010
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Research ArticleArticle

Expression and Localization of Rat Aldo-Keto Reductases and Induction of the 1B13 and 1D2 Isoforms by Phenolic Antioxidants

A. Kenneth MacLeod, Vincent P. Kelly, Larry G. Higgins, Michael O. Kelleher, Sally A. Price, Alison L. Bigley, Graham R. Betton and John D. Hayes
Drug Metabolism and Disposition February 1, 2010, 38 (2) 341-346; DOI: https://doi.org/10.1124/dmd.109.030544

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Research ArticleArticle

Expression and Localization of Rat Aldo-Keto Reductases and Induction of the 1B13 and 1D2 Isoforms by Phenolic Antioxidants

A. Kenneth MacLeod, Vincent P. Kelly, Larry G. Higgins, Michael O. Kelleher, Sally A. Price, Alison L. Bigley, Graham R. Betton and John D. Hayes
Drug Metabolism and Disposition February 1, 2010, 38 (2) 341-346; DOI: https://doi.org/10.1124/dmd.109.030544
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