Hydroxysteroid sulfotransferase (SULT2A) の発現はFXRにより抑制的に調節される Chenodeoxycholic Acid-mediated Activation of the Farnesoid X Receptor Negatively Regulates Hydroxysteroid Sulfotransferase

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著者

    • MIYATA Masaaki
    • Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
    • MATSUDA Yoshiki
    • Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
    • TSUCHIYA Hiroyuki
    • Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
    • KITADA Hirotaka
    • Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
    • AKASE Takanori
    • Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
    • SHIMADA Miki
    • Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
    • NAGATA Kiyoshi
    • Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
    • GONZALEZ Frank J.
    • Laboratory of Metabolism, National Cancer Institute, National Institutes of Health
    • YAMAZOE Yasushi
    • Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University

抄録

  Hydroxysteroid sulfotransferase catalyzing bile acid sulfation plays an essential role in protection against lithocholic acid (LCA)-induced liver toxicity. Hepatic levels of Sult2a is up to 8-fold higher in farnesoid X receptor-null mice than in the wild-type mice. Thus, the influence of FXR ligand (chenodeoxycholic acid (CDCA) and LCA) feeding on hepatic Sult2a expression was examined in FXR-null and wild-type mice. Hepatic Sult2a protein content was elevated in FXR-null and wild-type mice fed a LCA (1% and 0.5%) diet. Treatment with 0.5% CDCA diet decreased hepatic Sult2a to 20% of the control in wild-type mice, but increased the content in FXR-null mice. Liver Sult2a1 (St2a4) mRNA levels were reduced to 26% in wild-type mice after feeding of a CDCA diet, while no decrease was observed on Sult2a1 mRNA levels in FXR-null mice after CDCA feeding. A significant inverse relationship (r<sup>2</sup>=0.523) was found between hepatic Sult2a protein content and small heterodimer partner (SHP) mRNA level. PCN-mediated increase in Sult2a protein levels were attenuated by CDCA feeding in wild-type mice, but not in FXR-null mice. Human SULT2A1 protein and mRNA levels were decreased in HepG2 cells treated with the FXR agonists, CDCA or GW4064 in dose-dependent manners, although SHP mRNA levels were increased. These results suggest that SULT2A is negatively regulated through CDCA-mediated FXR activation in mice and humans.<br>

収録刊行物

  • Drug metabolism and pharmacokinetics  

    Drug metabolism and pharmacokinetics 21(4), 315-323, 2006-08-31 

    The Japanese Society for the Study of Xenobiotics

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各種コード

  • NII論文ID(NAID)
    10018042954
  • NII書誌ID(NCID)
    AA1162652X
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13474367
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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