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The molecular clock mechanism underlying the circadian rhythm of cellular metal level: interaction between molecular clock and cellular metal

Research Project

Project/Area Number 25670079
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionKyushu University

Principal Investigator

OHDO Shigehiro  九州大学, 薬学研究科(研究院), 教授 (00223884)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords薬学 / 生体リズム / 体内時計 / 時計遺伝子 / 金属元素
Outline of Final Research Achievements

Iron is an important biological catalyst and is critical for DNA synthesis during cell proliferation. Cellular iron uptake is enhanced in tumor cells to support increased DNA synthesis. In this study, we identified a 24-hr rhythm in iron levels in colon-26 tumors implanted in mice and the expression of iron regulatory protein 2 (IRP2). Furthermore, IRP2 regulated the 24-hr rhythm of transferrin receptor 1 (TfR1) mRNA expression post-transcriptionally by binding to RNA stem-loop structures known as iron-response elements. The transcription of IRP2 mRNA was promoted by circadian clock genes, including BMAL1 and CLOCK heterodimer. The expression of IRP2 in tumor cells was affected by the circadian organization of the molecular clock. Our findings suggest that circadian organization contributes to cell proliferation by regulating iron metabolism and may play a role in the circadian rhythm of other metals.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (7 results)

All 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) (of which Invited: 2 results)

  • [Journal Article] Modulation of peroxisome proliferator-activated receptor-α activity by bile acids causes circadian changes in the intestinal expression of Octn1/Slc22a4 in mice.2015

    • Author(s)
      Wada E, Koyanagi S, Kusunose N, Akamine T, Masui H, Hashimoto H, Matsunaga N, Ohdo S.
    • Journal Title

      Mol Pharmacol

      Volume: 87 Issue: 2 Pages: 314-322

    • DOI

      10.1124/mol.114.094979

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bile acid-regulated peroxisome proliferator-activated receptor-α (PPARα) activity underlies circadian expression of intestinal peptide absorption transporter PepT1/Slc15a1.2014

    • Author(s)
      Okamura A, Koyanagi S, Dilxiat A, Kusunose N, Chen JJ, Matsunaga N, Shibata S, Ohdo S.
    • Journal Title

      J Biol Chem.

      Volume: 289(36) Issue: 36 Pages: 25296-25305

    • DOI

      10.1074/jbc.m114.577023

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 24-Hour Rhythm of Aquaporin-3 Function in the Epidermis Is RegUlated by Molecular Clocks2014

    • Author(s)
      Naoya Matsunaga, Kazufumi Itcho, Kengo Hamamura, Eriko Ikeda, Hisako Ikeyama, Yoko Furuichi, Miyako Watanabe, Satoru Koyanagi, Shigehiro Ohdo
    • Journal Title

      Joumal of lnvestigative Dermatology

      Volume: (印刷中) Issue: 6 Pages: 1636-1644

    • DOI

      10.1038/jid.2014.13

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Renal circadian clock regulates the dosing-time dependency of cisplatin-induced nephrotoxicity in mice.2014

    • Author(s)
      Oda M, Koyanagi S, Tsurudome Y, Kanemitsu T, Matsunaga N, Ohdo S.
    • Journal Title

      Mol Pharmacol

      Volume: 85 Issue: 5 Pages: 715-722

    • DOI

      10.1124/mol.113.089805

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Circadian regulation of mTOR by the ubiquitin pathway in renal cell carcinoma2014

    • Author(s)
      Okazaki, H., Matsunaga, N., Fujioka, T., Okazaki, F., Akagawa, Y., Tsurudome, Y., Ono, M,. Kuwano, M., Koyanagi, S., and Ohdo, S.
    • Journal Title

      Cancer Res.

      Volume: 74 Issue: 2 Pages: 543-551

    • DOI

      10.1158/0008-5472.can-12-3241

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] がん細胞の薬剤感受性の概日リズム制御メカニズムと投薬のタイミング.2013

    • Author(s)
      大戸 茂弘 小柳 悟、松永 直哉
    • Organizer
      第86回 日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Chronopharmacological aspects of transporters2013

    • Author(s)
      大戸 茂弘 小柳 悟、松永 直哉
    • Organizer
      日本薬物動態学会 第28回年会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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