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Pathogenetic Significance of Lipid Peroxidation in Various Cell Injuries, with a Special Reference to the Investigation on Cell Biological Characteristics of Glutathione Peroxidase-an Anti-lipoperoxidative Agent.

Research Project

Project/Area Number 60440035
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionTokai University

Principal Investigator

WATANABE Keiichi  Professor, Department of Pathology Tokai University School of Medicine, 医学部・病理学, 教授 (00055865)

Co-Investigator(Kenkyū-buntansha) TSUTSUMI Yuitaka  Professor,Department of Pathology Tokai University School of Medicine, 医学部・病理学, 講師 (80138643)
MORIUCHI Tetsuya  Professor,Department of cell Biology Tokai University School of Medicine Assista, 医学部・細胞生物学, 講師 (20174394)
YOKOYAMA Seihichi  Associate Professor, Department of Surgery Tokai University School of Medicine A, 医学部・外科学, 助教授 (50096278)
MATSUZAKI shouhei  Associate Professor, Department of Internal Medicine Tokai University School of, 医学部・内科学, 助教授 (40110902)
OSAMURA Yoshiyuki  Associate Professor, Department of Pathology Takai University School of Medicine, 医学部・病理学, 助教授 (10100992)
Project Period (FY) 1985 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥19,700,000 (Direct Cost: ¥19,700,000)
Fiscal Year 1987: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1986: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1985: ¥15,500,000 (Direct Cost: ¥15,500,000)
KeywordsLipid Peroxidation / Glutathione Peroxidase / Cell Injury / 肝脂肪変性 / 脂肪肝 / 【CCl_4】 / 蛋白合成阻害剤 / hyperplastic nodule(過形成性結節) / グルタチオンペルオキシダーゼ(GSH-PO)セレン(Se) / GSH-PO合成誘導機構 / ミトコンドリア内局在 / (GSH-POの)アミノ酸配列
Research Abstract

Through a series of the experiments on lipoperoxidative cell injury or the enhanced lipid peroxidation in hepatocytes and peritoneal macrophages (M ), it was proved that the lipid peroxidation of certain degree elicited the increase of the glutathione peroxidase (GSH-PO), the effective lipid peroxides scavenger, in those cells. The other way around, the increase of GSH-PO synthesis in certain cell would strongly suggest that the increased lipid peroxidation may have been induced in those cells. On the basis of this notion, the immunohistochemical localization of GSH-PO in the atherosclerotic lesions of human arteries was investigated utilizing the anti human GSH-PO prepared in our laboratory after its immunohistochemical validity was checked by "Western" immunoblotting test. As a results, GSH-PO was specifically localized in "foamy cells" which are supposed to be originated from both the infiltrating M s and the intimal smooth muscle cells (SMC). Degenerated and/or deformed SMCs which are precursor to the "foamy cell" also showed the intense immunoperoxidase staining for the GSH-PO. Non-atherosclerotic arteries did not show such GSH-PO immunoperoxidase staining except the very weak staining shown in SMCs in their media.
In order to examine the course and the causative stimulation of the above changes, rabbits were fed with the high cholesterol diet (Oriental-Kohbo Co. Led) which was proved to induce typical atherosclerotic changes in their arteries for sure. The initial GSH-PO appeorance was observed in the foamy M s lined just beneath the endothelial cells in a monolayer. 2 weeks after the initiation of the diet. Sequentially, such GSH-PO positive cells increased their number, and GSH-positive SMCs gave their first appearance at 4th to 8th week.
Summerizing these results, the pathogenetic significance of the lipid peroxidation taking place in those "foamy cells" for atherosclerosis was stressed.

Report

(3 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • 1985 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] 渡辺 慶一: 日病会誌. 76. 39-74 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Keiichi Watanabe,Masanori Murakoshi: Tokai J Exp Clin Med. 11SUPPL. 105-109 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hideaki Hasegawa,Keiichi Watanabe,Tsuneaki Nakamura,Hiroshi Nagura: Cell and Tissue Research. 250(3). 521-529 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Masanori Murakoshi,Yoshiyuki Osamura,Keiichi Watanabe: Cell Structure and Function. 12. 181-186 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Masanori Murakoshi,Kozoh Ueno,Yoshiyuki Osamura,Keiichi Watanabe: Acta Histochem Sytochem. 20(3). 321-327 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Atushi Nakamura Kennichi Kakudo Keiichi Watanabe: Virshows Arch B. 53. 332-335 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Keiichi Watanabe: "Lipid Peroxidation and Cell Injury; The Role of Glutathione Peroxidase as the Regulatory Factor." Tr. Soc. Pathol. Jpn.76. 39-74 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Keiichi Watanabe: "Liped peroxidation and arachidonate cascade in macrophages with a special reference to the change of glutathione peroxidase, lipid peroxide scavenger." Tokai J Exp Clin Med. 11(suppl). 105-109 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hideaki Hasegawa, Keiichi Watanabe, Tsuneaki Nakamura,Hiroshi Nagura: "Immunocytochemical localization of alkaline phosphatase in absorptive cells of rat small intestine after colchicine treatment." Cell and Tissue Research. 250(3). 521-529 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Masanori Murakoshi, Yoshiyuki Osamura, Keiichi Watanabe: "Immunoelectron microscopy pinpoints glutathione-peroxidase(GSH-PO) in neonatal rat adrenal cortical cells." Cell Structure and Function. 12. 181-186 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Masanori Murakoshi, Kozoh Ueno, Yoshiyuki Osamura, Keiichi Watanabe: "Immunocytochemical localization of glutathione-peroxidase(GSH-PO) in the rat ovary." Acta Histochem Sytochem. 20(3). 321-327 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 渡辺慶一: 肝胆膵. 11. 861-868 (1985)

    • Related Report
      1986 Annual Research Report
  • [Publications] 村越正典: Biomedical Science. 6. 88-91 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 吉村真一: サイエンスフォーラム刊「トキシコロジーフォーラム」. 9. 289-294 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Sonoo Mizuiri: Renal Physiol Basel. 9. 249-256 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Masanori Murakoshi: Acta Histochem Cytochem. 19. 125-133 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Acta Histochemica et Cytochemica. 17-2. (1984)

    • Related Report
      1985 Annual Research Report
  • [Publications] J.Histochem.Cytochem.32-8. (1984)

    • Related Report
      1985 Annual Research Report
  • [Publications] "酵素抗体法" 学際企画, (1985)

    • Related Report
      1985 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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