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薬剤スクリーニングの簡素化-ヒト・ヒスチジン脱炭酸酵素

Research Project

Project/Area Number07557192
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section試験
Research Field General pharmacology
Research InstitutionTohoku University

Principal Investigator

OHTSTU Hiroshi  Tohoku University, Medicine, Assistant Professor, 医学部, 助手 (60250742)

Co-Investigator(Kenkyū-buntansha) YATSUNAMI Kimio  Japan Tobacio.Inc.Pharmacentical Basic Research Laboratories, Chief Researcher, 主席研究員
WATANABE Takehiko  Tohoku University, Medicine, Professor, 医学部, 教授 (70028356)
Project Period (FY) 1995 – 1996
Project Status Completed(Fiscal Year 1996)
Budget Amount *help
¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1996 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Keywordshistidine decarboxylase / mast cell / differantiation / hematopoictic cell / transcription / cell specificity / transcription facter
Research Abstract

Histidine decarboxylase (HDC) is the unique enzyme which catalyze the synthetic reaction of histamine from histidine in mammalian cells. Histamine is expressed exclusively in basophilic and mast cell lineage in hematopoietic cells, therefore we are interested in the mechanism of tissue specific expression of this gene. We prepared various reporter constructs and transfected them into verious cell lines and clarified no tissue specific element exists from 6 Kb upstream to 1 Kb downstream of this gene. We found tissue specific DNase I hypersensitive sites in the promoter region by genomic DNA blotting, suggesting that this region is easily approached by transcription factors for their gene expression. Moreover, many cytosine molecules were methylated in this promoter region in HDC-non-expressing cell lines. Therefore, the cell specific expression of HDC gene is thought to be confirred to the differences of chromatin structure and methylation pattern rather than those of trans-acting factors.
We also are interested in mouse HDC gene, because we can approach many physiological and pharmacological problem which could not be approached in human. We, first, constructed a plasmid that contains 1099 bases upstream of the transcription initiation site fused with luciferase gene and transfected this plaamid stably into P815 mouse mast cell line. With this plasmid, we reported the mechanism of how P815 cells was induced to express HDC gene in peritoneal cavity of syngenic BDF1 mouse (J.Biol.Chem.271,28439-28444). We are planning to elucidate the cis-acting element confering this inducibility using former stable transformant. By applying many kinds of medicine to this cell line and measuring the luciferase activity, we can assess the effect of these medicine on the transactivational activity of HDC gene. We are now under cloning of human stable transformant to be used for the assessment of activity of various medicine.

Report

(3results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report

Research Products

(9results)

All Other

All Publications

  • [Publications] Ohtsu,H.et al.: "Histidine Decarboxylase Expression in Mouse Mast Cell Line P815 is induced by Peritoneal Cavity Incubation" J.Biol.Chem.271(45). 28439-28444 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakagawa,S.et al.: "Identification of multiple regalatory elament of human L-Histidine Decarboxylase Gene" J.Biochem.121(5)(印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Chtsu, H.et at.: "Histidine Decarboxylase Expression in Mouse Mast Cell Line P815 is induced by Peritoneat Cavity Incubation" J.Biol.Chem.271(45). 28439-28444 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakagawa, S.et at.: "Identification of multiple regulatory element of human L-Histidine Decarboxylase Gene" J.Biochem.121(5)(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ohtsu, H. et al: "Histidine Decarboxylase Expression in Mouse Mast Cell Line P815 is induced by Peritoneal Cavity Incubation" J. Biol. Chem.271 (45). 28439-28444 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakagawa, S. et al: "Identification of multiple regulatory element of luunan L-Histicine Decarbcxylase Gone" J. Biochem.121 (5) (発表予定). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamauchi, K. et al.: "Molecular Biological Aspects of Human L-Histidine Decarboxylase" Advances in the Biosciences. 89. 177-196 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yatsunami, K. et al.: "Structure of the L-lristidine decarboxylase gene" J. Biol. Chem.269. 1554-1559 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] 大津浩 他1名: "GATA因子によるマスト細胞の分化制御" 造血因子. 6. 134-141 (1995)

    • Related Report
      1995 Annual Research Report

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Published : 1996-04-01   Modified : 2016-04-21  

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