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THE MECHANISM AND BIOSYNTHESIS OF BIOACTIVE LIPIDS

Research Project

Project/Area Number 04670158
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

IZUMI Takashi  TOKYO UNIV., DEPT.OF MEDICINE, ASSISTANT, 医学部(医), 助手 (70232361)

Co-Investigator(Kenkyū-buntansha) HONDA Zen-ichiro  TOKYO UNIV., DEPT.OF MEDICINE, ASSISTANT, 保健センター, 助手 (70238814)
SHIMIZIU Takao  TOKYO UNIV., DEPT.OF MEDICINE, PROFESSOR, 医学部(医), 教授 (80127092)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsBIOACTIVE LIPIDS / LEUKOTRIENE / PLATELET-ACTIVATING FACTOR / SYNTHETIC ENZYME / RECEPTOR / SIGNAL TRANSDUCTION / INACTIVATING ENZYME
Research Abstract

1. STUDY FOR LEUKOTRIENE BIOSYNTHESIS AND METABOLISM
A monoclonal antibody to LTC_4 synthase was developed, and using this antibody enzyme purification is now going on.
A mutagenesis study of LTA_4 hydrolase revealed that the active center for LTB_4 producing activity is different from that for aminopeptidase activity.
We showed that LTB_4 is inactivated by LTB_4-12-hydroxydehydrogenase in porcine kidney, and this enzyme was purified to apparent homogeneity.
2. STUDY FOR FUNCTION OF LEUKOTRIENE
Studies for cDNA cloning of leukotriene receptors are going on using frog oocyte expression system or mammalian cell expression system.
3. STUDY FOR PAR RECEPTOR
The presence of functionally active PAF receptor in rat brain have been indicated.
In a human eosinophilic leukemia cell line (EoL-1 cells), PAF receptor were induced during differentiation by sodium butyrate.
Studies on human PAF receptor gene revealed that two different promoter exist to produce two types of mRNA, namely leukocyte type and heart type.
In CHO cells transfected with PAF receptor, PAF activated MAP kinase and MAP kinase kinase.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Shimizu,T.: "Platelet Activating Factor Receptor and Signal Transduction." Biochem.Pharmacol.44. 1001-1008 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Bito,H.: "Platelet-Activating Factor(PAF)Receptor in Rat Brain:PAF Mobilizes Intracellular Ca^<2+> in Hippocampal Neurons." Neuron. 9. 1-10 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minami,M.: "Leukotriene A_4 hydrolase,a bifunctional enzyme:Distinction of leukotriene A4 hydrolase and aminopeptidase activities by site-directed mutagenesis at Glu-297." FEBS. 309. 353-357 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Izumi,T.: "Site-directed mutagenesis of leukotriene A_4 hydrolase:distinction of leukotriene A_4 hydrolase and aminopeptidase activities." J.Lipid Mediators. 6. 53-58 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori,M.: "Energy-dependent export of leukotriene B_4 in Xenopus oocytes." Biochim.Biophys.Acta. 1168. 23-29 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mutoh,H.: "Two different promoters direct expression of two distinct forms of mRNAs of human platelet-activating factor receptor." FEBS.322. 129-134 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yokomizo,T.: "Enzymatic Inactivation of Leukotriene B_4 by a Novel Enzyme Found in the Porcine Kidney." J.Biol.Chem.268. 18128-18135 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Honda,Z.: "Transfected Platelet-activating Factor Receptor Activates Mitogen-activated Protein(MAP)Kinase and MAP Kinase Kinase in Chinese Hamster Ovary Cells." J.Biol.Chem.269. 2307-2315 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Izumi,T.: "Frontiers and new horizons in amino acid reserch(ed.by K.Takai)" Elsevier(Amsterdam), 705 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimizu,T.: "Advances in Polyunsaturated Fatty Acids Research.(ed.by T.Yasugi,.et al)" Elsevier(Amsterdam), 294 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Simizu, T.: "Platelet Activating Factor Receptor and Signal Transduction." Biochem.Pharmacol.44. 1001-1008 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Bito, H.: "Platelet-Activating Factor(PAF) Receptor in Rat Brain : PAF Mobilizes Intracellular Ca^<2+> in Hippocampal Neurons." Neuron. 9. 1-10 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minami, M.: "Leukotriene A_4 hydrolase, a bifunctional enzyme : Distinction of leukotriene A_4 hydrolase and aminopeptidase activities by site-directed mutagenesis at Glu-297." FEBS. 309. 353-357 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Izumi, T.: "Site-directed mutagenesis of leukotriene A_4 hydrolase : distinction of leukotriene A_4 hydrolase and aminopeptidase activities." J.Lipid Mediators. 6. 53-58 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mori, M.: "Energy-dependent export of leukotriene B_4 in Xenopus oocytes." Biochim.Biophys.Acta. 1168. 23-29 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mutoh, H.: "Two different promoters direct expression of two distinct forms of mRNAs of human platelet-activating factor receptor." FEBS. 322. 129-134 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yokomizo, T.: "Enzymatic Inactivation of Leukotriene B_4 by a Novel Enzyme Found in the Porcine Kidney." J.Biol.Chem.268. 18128-18135 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Honda, Z.: "Transfected Platelet-activating Factor Receptor Activates Mitogen-activated Protein(MAP) Kinase and MAP Kinase Kinase in Chinese Hamster Ovary Cells." J.Biol.Chem.269. 2307-2315 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Izumi, T.: Biosynthesis of Leukotriene C_4 in "Frontiers and new horizons in amino acid research" (ed.by K.Takai). Elsevier(Amsterdam), 583-586 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimizu, T.: Bifunctional Roles of Leukotriene A_4 Hydrolase in "Advances in Polyunsaturated Fatty Acids Research." (ed.by T.Yasugi, et al). Elsevier(Amsterdam), 31-34 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mutoh,H.: "Two different promoters direct expression of two distinct forms of mRNAs of human platelet-activating factor receptor." FEBS.322. 129-134 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yokomizo,T.: "Enzymatic Inactivation of Leukotriene B_4 by a Novel Enzyme Found in the Porcine Kidney." J.Biol.Chem.268. 18128-18135 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Honda,Z.: "Transfected Platelet-activating Factor Receptor Activates Mitogen-activated Protein(MAP)Kinase and MAP Kinase Kinase in Chinese Hamster Ovary Cells." J.Biol.Chem.269. 2307-2315 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shimizu,T.: "Advances in Polyunsaturated Fatty Acids Research.(ed.by T.Yasug,.et al)" Elsevier(Amsterdam), 294 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shimizu,T.: "Platelet Activating Factor Receptor and Signal Transduction." Biochem.Pharmacol.44. 1001-1008 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Bito,H.: "Platelet-Activating Factor(PAF)Receptor in Rat Brain:PAF Mobilizes Intracellular Ca^<2+> in Hippocampal Newrons." Neuron. 9. 285-294 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Minami,M.: "Leukotriene A_4 hydrolase,a bifunctional enzyme:Distinction of leukotriene A_4 hydrolase and aminopeptidase activities by site-directed mutagenesis at Glu-297." FEBS. 309. 353-357 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Izumi,T.: "Site-directed mutagenesis of leukotriene A_4 hydrolase:distinction of leukotriene A_4 hydrolase and aminopeptidase activities." J.Lipid Mediators. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mori,M.: "Energy-dependent export of leukotriene B_4 in Xenopus oocytes." Biochim.Biophys.Acta. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Izumi,T.: "Frontiers and new horizons in amino acid reserch(ed.by Takai,K.)" Elsevier(Amsterdam), 705 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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