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Novel effects and mechanisms of action of heme and soy isoflavones

Research Project

Project/Area Number 16500503
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Eating habits, studies on eating habits
Research InstitutionKanazawa University (2005)
Tohoku University (2004)

Principal Investigator

OGAWA Kazuhiro  Kanazawa University, Graduate School of Medical Science, Associate Professor, 医学系研究科, 助教授 (30344659)

Co-Investigator(Kenkyū-buntansha) 武田 和久  東北大学, 大学院・医学系研究科, 助手 (30311559)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsheme oxygenase / heme iron / heme / isoflavone / polyamine / 生体防御
Research Abstract

Heme is widely used as a food chemical for iron supplementation. Heme is an essential molecule for us as prosthetic groups for hemoglobin and many other hemoproteins. Excess free heme is a pro-oxidant and toxic, and is degraded by heme oxygenase (HO) to iron, CO and biliverdin, which is rapidly converted to bilirubin, an antroxidant. There are two isozymes of HO, namely inducible HO-1 and constitutive 110-2. Induction of HO-1 is an important defense mechanism against oxidative stress, and some HO inhibitors have antitumor activity. In this project, I have been evalutated the effects and analyzed the mechanisms of action of food chemicals such as heme iron and soy isoflavones on heme catabolism, using various types of human cells.
Prolonged hypoxia decreased the expression level of HO-2 as well as that of HO-1, and these down-regulations of HOs were caused at both transcriptional and post-transcriptional levels. Down-regulation of 110-2 by siRNA induced the HO-1 expression, and HO-2 knock-down 1 under some conditions increased the intracellular heme content, suggesting the significance of HO-2 in the maintenance of cellular heme levels and in the regulation of HO-1 expression. Genistein, a soy isoflavone, inhibited the induction of HO-1 by heme and other chemicals, while daidzein, another soy isoflavone, did not inhibited the induction of HO-1 in some cases. Together with results of our other experiments, these inhibitory effects of isoflavones on HO-1 induction were suggested to be mediated by estrogen receptor-independent mechanism.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Products Report
  • Research Products

    (13 results)

All 2006 2005 2004

All Journal Article (10 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Hypoxia reduces the expression of heme oxygenase-2 in various types of human cell lines2006

    • Author(s)
      ZHANG, Yongzhao et al.
    • Journal Title

      FEBS Journal 273

      Pages: 3136-3147

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Down-regulation of heme oxygenase-2 is associated with the increased expression of heme oxygenase-1 in human cell lines2006

    • Author(s)
      DING, Yuanying et al.
    • Journal Title

      FEBS Journal 273

      Pages: 5333-5346

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia reduces the expression of heme oxygenase-2 in various types of human cell lines2006

    • Author(s)
      ZHANG, Yongzhao etal.
    • Journal Title

      FEBS Journal 273

      Pages: 3136-3147

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 核内受容体を介するイソフラボンの作用メカニズムの解明2004

    • Author(s)
      小川 和宏 ら
    • Journal Title

      大豆たん白質研究 7

      Pages: 125-129

    • NAID

      40006505906

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ヘム分解系-多彩な疾患への創薬標的-2004

    • Author(s)
      小川 和宏
    • Journal Title

      日本薬理学雑誌 124

      Pages: 360-362

    • NAID

      10014385128

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of heme oxygenase-1 and ligand-binding transcription factors by soybean isoflavones2004

    • Author(s)
      OGAWA, Kazuhiro et al.
    • Journal Title

      Soy Protein Research 7

      Pages: 125-129

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heme catabolic pathway as drug targets2004

    • Author(s)
      OGAWA, Kazuhiro
    • Journal Title

      Folia Pharmacologica Japonica 124

      Pages: 360-362

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-22004

    • Author(s)
      Adachi, Ishikawa, Hida, Matsumoto, Masuda, Date, Ogawa, Takeda et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 320

      Pages: 514-522

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of heme oxygenase-1 and ligand-binding transcription factors by soybean isoflavones2004

    • Author(s)
      Ogawa, Nagata, Suzuki, Konno, Shibahara, Yanagisawa
    • Journal Title

      Soy Protein Res., Japan 7

      Pages: 125-129

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ヘム分解系-多彩な疾患への創薬標的-2004

    • Author(s)
      小川 和宏
    • Journal Title

      日薬理誌 124

      Pages: 360-362

    • NAID

      10014385128

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] ヘムオキシゲナーゼ-1誘導剤、培地製造方法、移植用臓器の保存液製造方法および実験動物生産方法2005

    • Inventor(s)
      小川和宏
    • Industrial Property Rights Holder
      小川和宏
    • Patent Publication Number
      2005-298492
    • Filing Date
      2005-03-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] ヘムオキシゲナーゼ-1誘導剤、培地製造方法、移植用臓器の保存液製造方法および実験動物生産方法2005

    • Inventor(s)
      小川和宏
    • Industrial Property Rights Holder
      小川和宏
    • Industrial Property Number
      2005-072105
    • Filing Date
      2005-03-14
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] ヘムオキシゲナーゼ-1誘導剤、培地製造方法、移植用臓器の保存液製造方法および実験動物生産方法2005

    • Inventor(s)
      小川和宏
    • Industrial Property Rights Holder
      小川和宏
    • Industrial Property Rights Type
      特許
    • Filing Date
      2005-03-14
    • Acquisition Date
      2012-08-17
    • Related Report
      Products Report

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Published: 2004-04-01   Modified: 2017-02-24  

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