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Oxygen radical-induced tissue injury

Research Project

Project/Area Number 02557090
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionUNIVERSITY OF TOKYO

Principal Investigator

KUDO Ichiro  Univ. Tokyo, Associate Professor, 薬学部, 助教授 (30134612)

Co-Investigator(Kenkyū-buntansha) TAKAMURA Tadanobu  Eisai, Tsukuba Research Institute, Senior Researcher, 研究開発部, 主任研究員
ARAI Hiroyuki  Univ. Tokyo, Instructor, 薬学部, 助手 (40167987)
UMEDA Masato  Univ. Tokyo, Instructor, 薬学部, 助手 (10185069)
浜野 裕之  エーザイ株式会社, 研究開発部, 室長
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 1992: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1991: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1990: ¥7,000,000 (Direct Cost: ¥7,000,000)
KeywordsIschemia / Phospholipase A2 / liver injury / 酸素ストレス / 肝臓障害 / ホスホリパ-ゼA_2 / 血液凝固 / 虚血心筋 / 臨界ミセル濃度
Research Abstract

Phospholipid-hydrolyzing activities were examined in rat hearts with ischemia induced by occlusion of the left main coronary artery. When homogenates of ischemic heart were incubated in vitro at 37 ゚C, a significant amount of phosphatidylethanolamine (PE) was degraded, whereas the contents of other phospholipids did not change significantly. During the incubation, a stoichiometrical amount of lysoPE bearing mainly saturated fatty acids, whose composition resembled that of fatty acids detected at the sn-1 position in the glycerol backbone of heart PE, was formed concomitantly. No appreciable PE degradation was observed in homogenates prepared from nonischemic heart. No difference in phospholipase activities was found between ischemic and nonischemic heart homogenates when exogenous radioactive phospholipids were used as substrates. Anti-rat type II phospholipase A_2(PLA_2) antibody suppressed the degradation of PE observed in ischemic heart homogenates. These findings indicate that type II PLA_2 activity may be involved in the breakdown of endogenous PE in ischemic heart homogenates.
Activation of type II PLA_2, leading to hydrolysis of endogenous PE, was also observed in other oxygen radical-induced tissue injury, such as CCl_4-treated rat liver. Certain lipid-derived compound(s), which activated type II PLA_2, were detected in homogenate of CCl_4-treated liver. In the presence of lipids derived from CCl_4-treated liver, type II PLA_2 was significantly activated at lower (10^<-6> to 10^<-5> M) Ca^<2+> concentrations. Production of peroxidized lipids might explain the progressed breakdown of endogenous PE by type II PLA_2 in oxygen-injured tissues.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Makoto MURAKAMI: "Release of 14-kDa group-2 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Makoto MURAKAMI: "Molecular Nature of Phospholipases A_2 Involved in Prostaglandin I_2 Synthesis in Human Umbliical Vein Endothelial Cells" The Journal of Biological Chemistry. 268. 839-844 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Makoto Murakami, Ichiro Kudo, Yorimasa Suwa, and Keizo Inoue: "Release of 14-kDa group II phospholipase A2 from activated mast cells and its possible involvement in the regulation of the degranulation process" Eur. J. Biochem.209. 257-265 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mokoto Murakami, Ichiro Kudo, and Keizo Inoue: "Molecular nature of phospholipase A2 involved in prostaglandin I2 synthesis in human umbilical vein endothelial cells" J. Biol. Chem.268. 839-844 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ichiro Kudo and Keizo Inoue: "Review: Mammalian non-pancreatic phospholipase A2: Structure, properties, function" Biochemistry (in Japanese). 64. 1330-1344 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Makoto MURAKAMI: "Release of 14-kDa group-II Phospholipase A_2 from ativated 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 JOURANL 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_<>:構造,性状,機能" 生化学. 64. 1330-1344 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 村上 誠: "細胞外II型ホスホリパ-ゼA_2による肥満細胞でのアラキドン酸代謝物産生" FEBS Lett.294. 247-251 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 藤守 由美: "アラキドン酸高親和性ホスホリパ-ゼA_2の免疫的検出" J.Biochemistry. 111. 54-60 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 菊池 玲: "ラット虚血心筋における膜リン脂質の異常崩壊"

    • Related Report
      1991 Annual Research Report
  • [Publications] 高橋 勝彦: "哺乳動物II型ホスホリパ-ゼA_2の活性化機構"

    • Related Report
      1991 Annual Research Report
  • [Publications] 菊池 玲: "ラット虚血心筋における膜リン脂質の異常崩壊"

    • Related Report
      1990 Annual Research Report
  • [Publications] 笠 明美: "四塩化炭素誘導ラット肝障害における膜リン脂質の異常崩壊"

    • Related Report
      1990 Annual Research Report
  • [Publications] 高橋 勝彦: "高等動物14キロダルトンII型ホスホリパ-ゼA_2の活性化機構"

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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