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Regulation of transcription by heme with sperm reference to cell differentiation

Research Project

Project/Area Number 14370048
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 University, School of Medicine, Professor, 大学院・医学研究科, 教授 (60142931)

Co-Investigator(Kenkyū-buntansha) ODA Atsushi  Hokkaido University, School of Medicine, Associate Professor, 大学院・医学研究科, 講師 (50255436)
小川 和宏  東北大学, 大学院・医学系研究科, 助手 (30344659)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥6,400,000 (Direct Cost: ¥6,400,000)
Keywordsheme / Bach1 / globin / erythrocyte / platelet / hypoxia / 転写調節 / rac / シグナル伝達 / 赤血球分化 / 負の転写調節 / 造血細胞分化 / エリスロポエチン / 巨核球
Research Abstract

We have investigated Bach1, the first found mammalian transcriptional factor that contains heme. Our previous investigations reveals that the factor contains one mole of heme per one subunit, and that the DNA binding activity of Bach1 is negatively regulated by heme saturation. In other words, heme saturated Bach1 lose its binding activity against MARE site resulting in an available MARE site for another transcriptional factors such as Nrf2, NFE2 and so on.
It has been, however, not yet well elucidated the genes that are under the negative control in Bach1/heme system. In the present study, we have examined if hens oxygenase-1 gene, the key enzyme of home catabolism, which is well known to activated by its substrate, is under the control of Bach1/heme system or not. As was already expected, our data is clearly indicated that heme oxygenase-1 gene was negatively regulated through Bach1 binding to MARE site. Hereby, we elucidated for the first time the precise mechanism of here mediated activation of gene that is physiologically important to metabolize a huge amount of heme, a biologically harmful pro-oxidant.
In addition to heme oxygenase-1 gene, we have examined the regulation of beta-globin gene. It is well known that heme and globin syntheses for hemoglobin are coordinated ; i.e., there are no exceeded syntheses for heme and globin. The mechanism to regulate equal mole of heme and globin has not been well understood. Bach1 is one of the most possible mechanisms to control hemoglobin formation. Indeed, our observations demonstrated that MEAR site in globin gene ruled heme mediated upregulation via the loss of Bach1 binding activity. Thus, we can biosynthesize globin protein just equal to home in differentiating erythroid cells. In this way, we are free form dangerous pro-oxidant, heme, even through erythroid differentiation.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (38 results)

All 2005 2004 2003 2002 Other

All Journal Article (27 results) Book (1 results) Publications (10 results)

  • [Journal Article] WAVE/Scars in Platelets.2005

    • Author(s)
      Oda A et al.
    • Journal Title

      Blood (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] WAVE/Scars in Platelets.2005

    • Author(s)
      Oda A, Miki H, Wada I, Yamaguchi H, Yamazaki D, Suetsugu S, Nakajima M, Nakayama A, Okawa K, Miyazaki H, Matsuno K, Ochs HD, Machesky LM, Fujita H, Takenawa T
    • Journal Title

      Blood (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Signal Transduction and Cellular Functions of the TEL/ARG Oncoprotein.2005

    • Author(s)
      Okuda K, Oda A, Sato Y, Nakayama A, Fujita H, Sonoda Y, JD Griffin
    • Journal Title

      Leukemia (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Relationship between loperamide-induced sedative effect and digoxin pharmacokinetics in healthy Japanese subjects.2005

    • Author(s)
      Kobayashi, M., Fujita, H., et al.
    • Journal Title

      Pharmaceutical Research 22

      Pages: 413-418

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Heme positively regulates the expression of β-globin at the locus control region via the transcriptional factor Bach1 in erythroid cells.2004

    • Author(s)
      Tahara T et al.
    • Journal Title

      J Biol Chem 279

      Pages: 5480-5487

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Heme positively regulates the expression of b-globin at the locus control region via the transcriptional factor Bach1 in erythroid cells.2004

    • Author(s)
      Tahara T, Sun J, Nakanishi K, Yamamoto M, Mori H, Saito T, Fujita H, Igarashi K, Taketani S.
    • Journal Title

      J Biol Chem. 279

      Pages: 5480-5487

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nonylphenol enhances apoptosis induced by serum deprivation in PC12 cells.2004

    • Author(s)
      Aoki M, Kurasaki M, Saito T, Seki S, Hosokawa T, Takahashi Y, Fujita H, Iwakuma T
    • Journal Title

      Life Sci 74

      Pages: 2301-2312

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Heme positively regulates the expression of beta-globin at the locus control region via the transcriptional factor Bach1 in erythroid cells.2004

    • Author(s)
      Tahara T, Fujita H.et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 5480-5487

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nonylphenol enhances apoptosis induced by serum deprivation in PC12 cells.2004

    • Author(s)
      Aoki, M., Fujita, H, et al.
    • Journal Title

      Life Sci. 74

      Pages: 2301-2312

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CrkL directs ASAP1 to preripheral focal adhesions.2003

    • Author(s)
      Oda A et al.
    • Journal Title

      J Biol Chem 278

      Pages: 6458-6460

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bach 1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells.2003

    • Author(s)
      Kitamuro T et al.
    • Journal Title

      J Biol Chem 278

      Pages: 9125-9133

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] CrkL directs ASAP1 to preripheral focal adhesions.2003

    • Author(s)
      Oda A, Wada I, Miura K, Okawa K, Kadoya T, Kadoya T, Kato T, Nishihara H, Maeda M, Tanaka S, Nagashima K, Nishitani C, Masuno K, Ishino M, Machesky LM, Randazzo P, Fujita H
    • Journal Title

      J Biol Chem 278

      Pages: 6456-6460

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bach 1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells.2003

    • Author(s)
      Kitamuro T, Takahashi K, Ogawa K, Udono RF, Takeda K, Furuyama K, Nakayama M, Sun J, Fujita H, Hida W, Hattori T, Shirato K, Igarashi K, Shibahara S
    • Journal Title

      J Biol Chem 278

      Pages: 9125-9133

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Erythropoietin regulates tumor growth of human malignancies.32003

    • Author(s)
      Yasuda Y, Fujita Y, Matsuo T, Koinuma S, Hara S, Tazaki A, Onozaki M, Hashimoto M, Musha T, Ogawa K, Fujita H, Nakamura Y, Shiozaki H, Utsumi H
    • Journal Title

      Carcinogenesis 24

      Pages: 1021-1029

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A functional role of Stat3 in vivo megakaryopoiesis.2002

    • Author(s)
      Kirito K et al.
    • Journal Title

      Blood 99

      Pages: 3220-3227

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Calpin is a STAT3 and STAT5 protease.2002

    • Author(s)
      Oda A et al.
    • Journal Title

      Blood 99

      Pages: 1850-1852

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of gonadectomy on immunoreactivity for choline acetyltransferase in the cortex, hippocampus, and basal forebrain of adult male rats.2002

    • Author(s)
      Nakamura N, Fujita H, Kawata M
    • Journal Title

      Neuroscience 109

      Pages: 473-485

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Calpin is a STAT3 and STAT5 protease.2002

    • Author(s)
      Oda A, Wakao H, Fujita H
    • Journal Title

      Blood 99

      Pages: 1850-1852

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A functional role of Stat3 in vivo megakaryopoiesis.2002

    • Author(s)
      Kirito K, Osawa M, Morita H, Shimizu R, Yamamoto M, Oda A, Fujita H, Tanaka M, Nakajima K, Miura Y, Ozawa K, Komatsu N
    • Journal Title

      Blood 99

      Pages: 3220-3227

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Bcl-2 linked apoptosis due to increase in NO synthase in brain of SAMP10.2002

    • Author(s)
      Saito T, Maekawa K, Takahashi Y, Saitoh H, Hosokawa T, Fujita H, Kurasaki M
    • Journal Title

      Biochem Biophys Res Com 297

      Pages: 517-522

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effect of Au injection on the ceruloplasmin, metallothionein and 8-hydroxydeoxyguanosine of rat serum, kidney and liver.2002

    • Author(s)
      Saito S, Hiyamuta S, Kurasaki M, Hosokawa T, Saito T, Fujita H, Yoshida K
    • Journal Title

      Chemico-Biological Interactions 140

      Pages: 265-278

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Erythropoietin is involved in growth and angiogenesis in malignant tumors of emale reproductive organs.2002

    • Author(s)
      Yasuda Y, Fujita Y, Masuda S, Musha T, Ueda K, Tanaka H, Fujita H, Matsuo T, Nagao M, Sasaki R, Nakamura Y
    • Journal Title

      Carcinogenesis 23

      Pages: 1797-1805

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Heme-regulated transcription factor Bach1.2002

    • Author(s)
      Ogawa K, Igarashi K, Nishitani C, Shibahara S, Fujita H
    • Journal Title

      J Health SCI (invited review) 48

      Pages: 1-6

    • NAID

      110003655085

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lead, Chemical Porphyria, and Heine as a Biological Mediator.2002

    • Author(s)
      H.Fujita, C.Nishitani, K.Ogawa
    • Journal Title

      Tohoku J.Exp.Med. (invited review) 196

      Pages: 53-64

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulatory heme and trichloroethylene intoxication : A possible explanation of the case of "A Civil Action".2002

    • Author(s)
      H.Fujita, C.Nishitani, K.Ogawa
    • Journal Title

      Environ.Health Prevent.Med. (invited review) 7

      Pages: 103-112

    • NAID

      110002694774

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] WAVE/Scars in Platelets.

    • Author(s)
      Oda A, Fujita H, et al.
    • Journal Title

      Blood (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Signal transduction and cellular functions of the TEL/ARG oncoprotein

    • Author(s)
      Oda A, Fujita H, et al.
    • Journal Title

      Leukemia (in press)

    • Related Report
      2004 Annual Research Report
  • [Book] 分子予防環境医学:生命科学研究の予防・環境医学への統合2003

    • Author(s)
      藤田博美, 西谷千明
    • Total Pages
      768
    • Publisher
      分子予防環境医学研究会編
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] A.Oda, I.Wada, K.et al.: "CrkL directs ASAP1 to preripheral focal adhesions"J.Biol.Chem.. 278. 6456-6460 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tahara T, Sun J et al.: "Heme positively regulates the expression of beta-globin at the locus control region via the transcriptional factor Bach1 in erythroid cells"J Biol Chem.. 279. 5480-5487 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 小田淳, 西谷千明, 藤田博美: "血小板顆粒放出機構"血管. 26. 39-43 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 藤田博美, 西谷千明: "分子予防環境医学:生命科学研究の予防・環境医学への統合"本の泉社、分子予防環境医学研究会編. 768 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] N.Nakamura, H.Fujita, M.Kawata: "Effects of gonadectomy on immunoreactivity for choline acetyltransferase in the cortex, hippocampus, and basal forebrain of adult male rats"Neuroscience. 109巻. 473-485 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Oda, H.Kawao, H.Fujita: "Calpin is a STAT3 and STAT5 protease"Blood. 99巻. 1850-1852 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Kirito, M.Osawa, H.Morita et al.: "A functional role of Stat3 in vivo megakaryopoiesis"Blood. 99巻. 3220-3227 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Yasuda, Y.Fujita, S.Masuda et al.: "Erythropoietin is involved in growth and angiogenesis in malignant tumors of female reproductive organs"Carcinogenesis. 23巻. 1797-1805 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Kitamuro, K.Takahashi, K.Ogawa et al.: "Bach 1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells"J. Biol. Chem.. 278巻. 9123-9133 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Fujita, C.Nishitani, K.Ogawa: "A possible explanation of the of "A Civil Action""Environ. Health Prevent. Med.. 7巻. 103-112 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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