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Evaluation of toxicities of porphyrin derivatives and its possible application

Research Project

Project/Area Number 13557028
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Hygiene
Research InstitutionHokkaido University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) IGARASHI Kazuhiko  Hiroshima Univ.School of Med., Prof., 医学部, 教授 (00250738)
SHIBAHARA Shigeki  Tohoku Univ.School of Med., Prof., 大学院・医学系研究科, 教授 (70206142)
SATO Haruo  Sato Inst.Pharmaceutical Res., Director, 所長(研究職)
OGAWA Kazuhiro  Tohoku Univ.School of Med., Instructor, 大学院・医学系研究科, 助手 (30344659)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2002: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2001: ¥7,100,000 (Direct Cost: ¥7,100,000)
Keywordsmetalloporthyrin / heme oxygenase / Bach1 / Nrf2 / transcriptional control / cell differentiation / erythroid cells / ヘム / NO供与体 / ポルフィリン / ヘムオキシゲナーゼ-1 / 転写因子 / 低酸素応答 / 金属 / 白血病発症 / NFE2 / 造血細胞分化
Research Abstract

Evaluation of porphyrin derivatives on lives were carried out in the points of effects on cell differentiation as well as on transcription. We, evidenced that Bach1 is the first heme-controlled transcriptional factor in vertebrates. Bach1 is shown to be regulated heme oxygenase-1, which is one of the members of defense system against chemical hazards. Thus, it seems to be possible the evaluation of toxicity via Bach1. In addition, Bach1 also regulates erythroid cell differentiation through globin ge nes. The function of Bach1 can be exchanged by metalloporphyrins other than heme, suggesting some porphyrin derivatives could be applied as drugs to control differentiation.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (47 results)

All Other

All Publications (47 results)

  • [Publications] A.Ogawa et al.: "Heme mediates de-repression of Maf recognition element through direct binding to transcription repressor Bach1."EMBO J.. 20. 2835-2843 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Yasuda et al.: "Inhibition of erythropoietin signalling destroys xenografts of ovarian and uterine cancers in nude mice."Brit.J.Cancer. 84. 836-843 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Endo et al.: "Stem cell factor protects c-kit Positive human primary erythroid cells from apoptosis."Exp.Hematol.. 29. 833-841 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Nakamura et al.: "Effects of gonadectomy on immunoreactivity for choline acetyltransferase in the cortex, hippocampus, and basal forebrain of adult male rats."Neurosci.. 109. 473-485 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Oda et al.: "Calpin is a STAT3 and STAT5 protease."Blood. 99. 1850-1852 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Kirito et al.: "A functional role of Stat3 in vivo megakaryopoiesis."Blood. 99. 3220-3227 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Saito et al.: "Bcl-2 linked apoptosis due to increase in NO synthase in brain of SAMP10."Biochem.Biophys.Res.Comm.. 297. 517-522 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Saito et al.: "The effect of Au injection on the ceruloplasmin, metallothionein and 8-hydroxydeoxyguanosine of rat serum, kidney and liver."Chemico-Biological Interactions. 140. 265-278 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Yasuda et al.: "Erythropoietin is involved in growth and angiogenesis in malignant tumors of female reproductive organs."Carcinogenesis. 23. 1797-1805 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ogawa et al.: "Heme-regulated transcription factor Bach1."J.Health Sci. (invited review). 8. 1-6 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Fujita et al.: "Lead, Chemical Porphyria, and Heme as a Biological Mediator."Tohoku J.Exp.Med., (invited review).. 196. 53-64 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Fujita et al.: "Regulatory heme and trichloroethylene intoxication : A possible explanation of the case of "A Civil Action"."Environ.Health Prevent.Med. (invited review).. 7. 103-112 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Oda et al.: "CrkL directs ASAP1 to preripheral focal adhesions."J.Biol.Chem.. 278. 6456-6460 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Kitamuro et al.: "Bach1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells."J.Biol.Chem.. 278. 9125-9133 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Yasuda et al.: "Erythropoietin regulates tumor growth of human malignancies."Carcinogenesis. 24. 1021-1029 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ogawa, J.Y.Sun, S.Taketani, O.Nakajima, C.Nishitani, S.Sassa, N.Hayashi, M.Yamamoto, S.Shibahara, H.Fujita, K.Igarashi: "Heme mediates de-repression of Maf recognition element through direct binding to transcription repressor Bach 1."EMBO J.. 20. 2835-2843 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Yasuda, T.Musha, H.Tanaka, Y.Fujita, H.Fujita, H.Utsumi, T.Matsuo, S.Masuda, M.Nagao, R.Sasaki, Y.Nakamura: "Inhibition of erythropoietin signaling destroys xenografts of ovarian and uterine cancers in nude mice."Brit.J.Cancer. 84. 836-843 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Endo, A.Oda, I.Satoh, Y.Haseyama, M.Nishio, K.Koizumi, H.Takashima, K.Fujimoto, Y.Amasaki, H.Fujita, T.Koike, K.Sawada: "Stem cell factor protects c-kit Positive human primary erythroid cells from apoptosis."Exp.Hematol. 29. 833-841 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [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. 473-485 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Oda, H.Wakao, H.Fujita: "Calpin is a STAT3 and STAT5 protease."Blood. 99. 1850-1852 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Kirito, M.Osawa, H.Morita, R.Shimizu, M.Yamamoto, A.Oda, H.Fujita, M.Tanaka, K.Nakajima, Y.Miura, K.Ozawa, N.Komatsu: "A functional role of Stat3 in vivo megakaryopoiesis."Blood. 99. 3220-3227 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Saito, K.Maekawa, Y.Takahashi, H.Saitoh, T.Hosokawa, H.Fujita, M.Kurasaki: "Bcl-2 linked apoptosis due to increase in NO synthase in brain of SAMP10."Biochem.Biophys.Res.Comm.. 297. 517-522 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Saito, S.Hiyamuta, M.Kurasaki, T.Hosokawa, T.Saito, H.Fujita, K.Yoshida: "The effect of Au injection on the ceruloplasmin, metallothionein and 8-hydroxydeoxyguanosine of rat serum, kidney and liver."Chemico-Biological Interactions. 140. 265-278 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Yasuda, Y.Fujita, S.Masuda, T.Musha, K.Ueda, H.Tasaka, H.Fujita, T.Matsuo, M.Nagao.R.Sasaki, Y.Nakamura: "Erythropoietin is involved in growth and angiogenesis in malignant tumors of female reproductive organs."Carcinogenesis. 23. 1797-1805 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ogawa, K.Igarashi, C.Nishitani, S.Shibahara, H.Fujita: "Heme-regulated transcription factor Bach 1."J.Health Sic.(invited review). 48. 1-6 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Fujita, C.Nishitani, K.Ogawa: "Lead, Chemical Porphyria, and Heme as a Biological Mediator."Tohoku J.Exp.Med.(invited review). 196. 53-64 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Fujita, C.Nishitani, K.Ogawa: "Regulatory heme and trichloroethylene intoxication : A possible explanation of the case of "A Civil Action"."Environ.Health Prevent.Med.(invited review). 7. 103-112 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Oda, I.Wada, K.Miura, K.Okawa, T.Kadoya, T.Kadoya, T.Kato, H.Nishihara, M.Maeda, S.Tanaka, K.Nagashima, C.Nishitani, K.Masuno, M.Ishino, L.M.Machesky, P.Randazzo, H.Fujita: "CrkL directs ASAP1 to preripheral focal adhesions."J.Biol.Chem.. 278. 6456-6460 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Kitamuro, K.Takahashi, K.Ogawa, R.F.Udono, K.Takeda, K.Furuyama, M.Nakayama, J.Sun, H.Fujita, W.Hida, T.Hattori, K.Shirato, K.Igarashi, S.Shibahara: "Bach 1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells."J.Biol.Chem.. 278. 9125-9133 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Yasuda, Y.Fujita, T.Matsuo, S.Koinuma, S.Hara, A.Tazaki, M.Onozaki, M.Hashimoto, T.Musha, K.Ogawa, H.Fujita, Y.Nakamura, H.Shiozaki, H.Utsumi: "Erythropoietin regulates tumor growth of human malignancies."Carcinogenesis. 24. 1021-1029 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Kitamuro, K.Takahashi et al.: "Bach 1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells"J.Biol.Chem. 278. 9125-9133 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Yasuda, Y.Fujita et al.: "Erythropoietin regulates tumor growth of human malignancies"Carcinogenesis. 24. 1021-1029 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 藤田博美, 西谷千明, 中島美寧博: "鉄の分子栄養学"日本衛生学雑誌. 58. 248-253 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 藤田博美: "予防医学事典"朝倉書店、松島綱治、酒井敏行、石川昌、稲寺秀邦(編)(印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shibahara S, Kitamuro T, et al.: "Heme degradation and human disease : diversity is the soul of life"Antioxid Redox Signal. 4. 593-602 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤田 博美: "生体防御に関わる蛋白質"日衛誌. 56. 603-605 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤田 博美: "中毒におけるヘム代謝系-酵素阻害から転写障害へ"医学のあゆみ. 202. 915-917 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Ogawa, K.Igarashi, C.Nishitani et al.: "Heme-regulated transcription factor Bach1"J. Health Sic.. 48. 1-6 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Fujita, C.Nishitani, K.Ogawa: "Lend, Chemical Porphyria, and Heme as a Biological Mediator"Tohoku J.Exp.Med.. 196. 53-64 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitamuro T, Takahachi K, Ogawa K, et al.: "Bach 1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells"J.Biol chem. 278. 9125-9133 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] K. Ogawa, et al.: "Heme mediates de-repression of Maf recognition element through direct binding to transcription repressor Bach1"EMBO J. 20. 2835-2843 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y. Yasuda, et al.: "Inhibition of erythropoietin signalling destroys xenografts of ovarian and uterine cancers in nude mice"Brit. J. Cancer,. 84. 836-843 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A. Oda, et al.: "Calpin is a STAT3 and STAT5 protease"Blood,. 99. 1850-1852 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] K. Ogawa, et al.: "Heme-regulated transcription factor Bach1"J. Health Sic.,. 48. 1-6 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] H. Fujita, et al.: "Lead, Chemical Porphyria, and Heme as a Biological Mediator"Tohoku J. Exp. Med.. in press. (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] H. Fujita, et al.: "Regulatory heme and trichloroethylene intoxication : A possible explanation of the case of "A Civil Action""Environ. Health Prevent. Med.. in press. (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 竹谷 茂、ら: "内海 耕造・井上 正康編、ミトコンドリアとヘム・鉄代謝、「新ミトコンドリア学」"共立出版. 48-55 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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