薬物代謝酵素の発現誘導におけるマイクロRNAの関与  [in Japanese] Involvement of MicroRNA in the Induction of Drug-metabolizing Enzymes  [in Japanese]

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Author(s)

    • 志津 怜太 Shizu Ryota
    • 昭和大学薬学部毒物学教室 Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University
    • 沼澤 聡 Numazawa Satoshi
    • 昭和大学薬学部毒物学教室 Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University
    • 吉田 武美 Yoshida Takemi
    • 昭和大学薬学部毒物学教室 Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University

Abstract

  MicroRNAs (miRNAs) are small noncoding RNAs of about 20 nucleotides in length and participate in the post-transcriptional regulation of gene expression. Accumulating evidence indicates that miRNA binds to 3′-UTR of its target mRNAs and thereby destabilizes the transcripts or suppresses the translation. It is expected that miRNAs could have diverse functions and therefore play a role in the gene expression caused by the drug treatment, which have yet to be determined. Demonstration of the participation of specific miRNA in the drug-mediated gene expression would make it a biomarker for the toxicological assessment and help an understanding of molecular machinery of the drug-drug interaction. Under these backgrounds, we investigated the change of miRNAs in the liver of mice treated with phenobarbital, a typical inducer for drug-metabolizing enzymes, and demonstrate the participation of miRNAs in the phenobarbital-regulated gene expression. We investigated the relationship between phenobarbital-mediated changes in miRNA and mRNA by using Agilent miRNA microarray and DNA microarray, followed by real time RT-PCR. From these experiments, it was suggested that the phenobarbital-induced changes in cyp2c29 and mrp3 are regulated by miR-30a and miR-29b, respectively. In addition, we obtained evidence that indicates a phenobarbital-mediated decrease in miR-122, a highly abundant liver-specific miRNA, leads to the activation of the transcription factor CAR and thereby induces drug-metabolizing enzymes.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 132(3), 311-318, 2012

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130001872026
  • NII NACSIS-CAT ID (NCID)
    AN00284903
  • Text Lang
    JPN
  • ISSN
    0031-6903
  • NDL Article ID
    023549581
  • NDL Call No.
    Z19-411
  • Data Source
    NDL  J-STAGE 
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