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Molecular Mechanisms Involved in Oxygen Sensing by Heme.

Research Project

Project/Area Number 10044230
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionHokkaido University

Principal Investigator

FUJITA Hiroyoshi  Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (60142931)

Co-Investigator(Kenkyū-buntansha) FUJII Yoshiaki  Tohoku Univ., Grad.School of Science, Prof., 大学院・理学研究科, 教授 (00098146)
高橋 徹  岡山大学, 医学部, 助手 (40252952)
高橋 恭子  北海道大学, 医学部, 助手 (50292008)
GASSMANN Max  チューリッヒ大学, 医学部, 研究班長
FANDREY Joac  リューベック医大, 医学部, 上級講師
佐々 茂  ロックフェラー大学, 研究室, 室長
SYTKOWSKI Ar  ハーバード大学, 医学部, 准教授
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
KeywordsHeme / Oxygen Sensing / Heme Oxygenase / Transcription / 遺伝性ヘモクロマトージス / 晩発性皮膚ポルフィリン症 / 鉄芽球性貧血患者 / HLA-B27 / ヘムオキシゲナーゼ-1 / 赤血球系 / ヘム合成系 / 環境応答
Research Abstract

Main aim of this project is to elucidate the biological significances of heme, with special reference to the mechanisms of diseases. One of the important results of this year is the elucidation of protective effect of heme oxygenase induction against acute renal failue. In addition, heme metabolism itself controlled the onset of side effect, hepatic disorder, by halothane.
Therefore, the mechanism to regulate heme metabolism by heme itself seems to be one of the key step to elucidate the significance of the compound. Although no remarkable finding about the heme-directed gene regulation in mammals has been reported until today, we found a new transcription factor, Bach1, is the candidate. We observed the molecular mechanism of heme to regulate Bach1 fanction and revealed the Bach1-heme mediated control of
heme oxygenase-1 gene.
These findings were presented in the International Symposium on the Regulation of Hematopoiesis in response to Environmental stress, held in Sapporo, from October 17 to 18, 2000 (chaired by H.Fujita). In the symposium, our findings on Bach1 is highly evaluated, and nowadays it is going to in press in the EMBO J.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report

Research Products

(22 results)

All Other

All Publications (22 results)

  • [Publications] H.Shimizu,T.Takahashi,T.Suzuki et al.: "Protective effect of heme oxygenase induction in ischemic renal failure"Crit.Care.Med.. 28. 809-817 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Okada,T.Takahashi A.Yamasaki et al.: "Prevention of halothan-induced hepatotoxicity by hemin pretreatment."Biochem.Pharmacol.. 59. 871-880 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Sassa and H.Fujita: "Regulation of Heme Biosynthesis by Hormone, Drugs and Environmental Chemicals. (ed.by Piper)"CRC Press (in press). 1000 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Shimizu, T.Takahashi, T,Suzuki et al: "Prpttective effect of heme ozygenase induction in ischemic renal failure"Crit.Care.Med.. 28. 809-817 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Okada, T.Takahashi. A,Yamasaki et al: "Prevention of halothan-induced hepatotoxicity by hemin pretreatment"Biochem. Pharmacol.. 59. 871-880 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Sassa, and H.Fujita: "Regulation of Heme Biosynthesis by Hormone, Drugs and Environmental chemicals.(ed.by Piper)"CRC Press (in press). 1000 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Shimizu, T.Takahashi,T.Suzuki et al.: "Protective effect of heme oxygenase induction in ischemic renal failure"Crit. Care. Med.. 28. 809-817 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Okada, T.Takahashi A.Yamasaki et al.: "Prevention of halothan-induced hepatotoxicity by hemin pretreatment"Biochem. Pharmacol.. 59. 871-880 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Sassa and H.Fujita: "Regulation of Heme Biosynthesis by Hormone, Drugs and Environmental Chemicals. (ed, by Piper)"CRC Press (in press). 1000 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] K. Takahashi, et al.: "Suppression of heme oxygenase-1 mRNA expression by interferon-g in human glioblastoma cells"J. Neurochem. 72. 2356-2361 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] E. Hara, et al.: "Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors"Biochem. Pharmacol. 58. 227-236 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Odaka, et al.: "Prevention of halothane-induced hepatotoxicity by hemin pretreatment : The protective role of heme oxygenase-1 induction"Biochem. Phamacol. 59. 871-880 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Shimizu, et al.: "Protective effect of heme oxygenase induction in ischemic acute renal failure"Crit. Care Med. in press. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Furuyama, et al.: "Absence of C282Y and H63D mutations of the hemochromatosis gene in Japanese patients with sideroblastic anemia"Amer. J. Hematol.. 61. 276 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Furuyama, et al.: "Extreme rare association of HFE mutations with porphyria cutanea tarda in Japanese patients"Hepatology. 30. 1532-1533 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Fujita: ""Current Protocols in Toxicology", M.Maines (ed.-in-chief)"(分担執筆)John Wiley & Sons (New York). 約1,500 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Harigae,N.Suwabe,P.H.Weinstock et al.: "Deficient heme and globin synthesis in ES cells lacking the erythroid-specific δ-aminolevulinate synthase gene." Blood. 91. 798-805 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Nagai,K.Igarashi,J.Akasaka et al.: "Regulation of NF-E2 Activity in Erythroleukemia Cell Differentiation." J.Biol.Chem.278. 5358-5365 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 藤田博美、竹谷茂ほか: "環境変動と分子応答" 環境科学会誌. 11. 183-192 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 藤田博美、島田薫ほか: "ヘム合成障害の分子遺伝学" ポルフィリン. 7. 1-32 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 藤田博美、小川和宏: "環境と健康(II)" へるす出版(東京), 310 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 藤田博美、小川和宏ほか: "図説・分子病態学 改訂2版" 中外医学社(東京), 510 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-03-31   Modified: 2016-04-21  

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