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Biological functions of mammalian non-pacreatic type Phospholipase A_2

Research Project

Project/Area Number 04404081
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionUniversity of Tokyo

Principal Investigator

INOUE Keizo  Univ.of Tokyo, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30072937)

Co-Investigator(Kenkyū-buntansha) AOKI Junken  Univ.of Tokyo, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (20250219)
ARAI Hiroyuki  Univ.of Tokyo, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (40167987)
梅田 真郷  東京大学, 薬学部, 助手 (10185069)
工藤 一郎  東京大学, 薬学部, 助教授 (30134612)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥17,500,000 (Direct Cost: ¥17,500,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥8,500,000 (Direct Cost: ¥8,500,000)
KeywordsPhospholipase A_2 / Prostaglandins / Inflammation / Mast cell / Degranulation / Calcium ion / platelet activating factor / lissencephaly / ホスホリパーゼ / 酸化リン脂質 / セリンエステラーゼ / PAF受容体 / ヒト無脳回症 / WD-40リピート / 脳 / PAF / 酸化脂肪酸 / リポポリサッカライド / TNF / 肝細胞 / 繊維芽細胞 / アラキドン酸 / ロイコトリエン
Research Abstract

Mammalian cells are known to posseces several type of phospholipase A2. Group II phospholipase A2 was detected in appreciable amounts in rat perioneal mast cells. It was found that the enzyme was is secreted into medium upon stimulation of the cells. The degranulation and eicosanoid production by mast cells are significantly suppressed by the inhibitors of group II phospholipase A2. These observation may suggest that this type of phospholipase A2 play an role in the progression of the degranulation process. A cytosolic phospholipiase A2 with a molecular weight of 85kDa is thought to be a rate limiting enzyme for the production of eicosanoids and leukotrienes. We have discovered that the enzyme has not only phospholipase A2 activity but also lysophospholipase activity. The lysophospholipids produced concomitant with the relase of arachidonaic acid is toxic to the cells because of its detergent-like nature. The cytosolic 85kDa phospholipase A2 may scavenge such lipids by its intrinsic lysophospholipiase activity.
Instead of Ca2+-dependent phospholipase A2 as mentioned above, we have discovered Ca2+-independent phospholipase A2 from mammalian brain. Moreover, we have succeeded in purification and cDNA cloning of the enzyme Unexpectedly, the gene encoding fothe one of the subunit is identical with the causative gene for the Miller-Dieker lissencephaly. This inherited syndrome caused a formation of smooth brain and a death in early age These results suggest that intrascellular phospholipase may play an essental role in the development of central nervous system.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Murakami M.: "Molecular Nature of phospholipase A_2 involved in prostaglandin I_2 synthesis in human umbilical vein endothetial cells" J.Biol.Chem.268. 839-844 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Asaoka: "Possible role of mammalian secretory groupII phospholipase A_2 in T-lymphocyte activation" Proc.Natl.Acad.Sci.USA. 90. 716-719 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Murakami M.: "Trigering of degranulation in mast cells by exogenous typeII phospholipase A_2" J.Immunol.151. 5675-5684 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hattori M.: "Purification and characterization of bovine brain plateletactivating factor acetylhydrolase" J.Biol.Chem.268. 18748-18753 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hattori M.: "Miller-Dieker Lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase" Nature. 370. 216-218 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hattori M.: "The catalytic subunit of bovine brain platelet-activating tactor is a novel type of Serine esterase" J.Biol.Chem.269. 23150-23155 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 工藤一郎,井上圭三: "高等動物非膵臓型ホスホリパーゼA_2:構造、性状、機能" 日本生化学会「生化学」, 15 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 田中和重,有田斉,井上圭三: "ホスホリパーゼA_2阻害剤-新しいタイプの抗炎症剤としての展望" 共立出版「蛋白質、核酸、酵素」, 13 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Murakami, I.Kudo and K.Inoue: ""Molecular nature of phospholipases A2 involved in prostaglandin I2 synthesis in human umbilical vein endothelial cells. Possible participation of cytosolic and extracellular type II phospholipases A2"" J.Biol.Chem.268. 839-844 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Asaoka, K.Yoshida, Y.Sasaki, Y.Nishizuka, M.Murakami, I.Kudo and K.Inoue: ""Possible role of mammalian secretory group II phospholipase A2 in T-lymphocyte activation : implication in propagation of inflammatory reaction"" Proc.Natl.Acad.Sci.USA. 90. 716-719 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Murakami, N.Hara, I.Kudo and K.Inoue: ""Triggering of degranulation in mast cells by exogenous type II phospholipase A2"" J.Immunol.151. 5675-5684 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Hattori, H.Arai and K.Inoue: ""Purification and characterization of bovine brain platelet-activating factor acetylhydrolase"" J.Biol.Chem.268. 18748-18753 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Hattori, H.Adachi, M.Tsujimoto, H.Arai and K.Inoue: ""Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase"" Nature. 370. 216-218 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayoshi Fukasawa, Kotaro Hirota, Hideki Adachi, Keiko Mimura, Kimiko Murakami-Murafushi, Masafumi Tsujimoto, Hiroyuki Arai and Keizo Inoue: "Chinese hamster ovary cells expressing a novel type of acetylated low density Lipoprotein receptor" J.Biol.Chem.270. 1921-1927 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] I.Kudo, K.Inoue: ""Mammalian non-pancreatic phospholipase A_2 : Structure, function and diversity."" Seikagaku. 64. 1330-1344 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Tanaka, H.Arata, K.Inoue: ""Phospholipase A_2 inhibitors-Prospect for new type of anti-inflammatory drug."" Protein, Nucleic acid, Enzyme. 38. 353-365 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hattori,M.: "Miller-Dieker lissencephaly gene encodes a subunit" Nature. 370. 216-218 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Inoue,K.: "PAF acetylhydrolase from mammalian tissues" J.Lipid Mediators. 10. 13-16 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hattori,M.: "The Catalytic Subunit of Bovine Brain Platelet-activating factor" J.Biol.Chem.269. 23150-23155 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shikano,M.: "Complete discrimination of docosahexaencoate from arachidonate" Biochion,Biophys,Acta. 1212. 211-216 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 須賀比奈子 他: "Participation in cellular prostaglandin synthesis of typeII PLA_2" Eur.J.Biochemistry. 218. 807-813 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 藤守由美 他: "Characterization of lysophospholipase cctivity expressed by cPLA_2" Eur.J.Biochemistry. 218. 629-635 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 村上誠 他: "Triggering of degranulation in mast cells by typeII PLA_2" J.Immunology. 151. 5675-5689 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 朝丘 他: "Possible role of typeII PLA_2 in T-lymphocyte activation" Proc.Natl.Acad.Sci. 90. 716-719 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 村上誠 他: "Molecular nature of PLA_2 involved in PGI_2 synthos's in HUVEC" J.Biol.Chemistry. 268. 839-844 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Makoto MURAKAMI: "Release of 14-kDa group-II phospholipase A_2 from activated mast cells and its possible involvement in the regulation of the degranulation process" Eur.J.Biochem.209. 257-265 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Makoto MURAKAMI: "Molecular Nature of Phospholipases A_2 Involved in Prostaglandin I_2 Synthesis in Human Umbilical Vein Endothelial Cells" THE JOURNAL OF BIOLOGICAL CHEMISTRY. 268. 839-844 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 工藤 一郎: "高等動物非膵型ホスホリパーゼA_2:構造,性状,機能" 生化学. 64. 1330-1344 (1992)

    • Related Report
      1992 Annual Research Report

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

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