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Pathophysiological role of lipid molecules produced by 12/l5-lipoxygenase

Research Project

Project/Area Number 12470024
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionKanazawa University

Principal Investigator

YOSHIMOTO Tanihiro  Kanazawa University, Pharmacology, Professor, 大学院・医学系研究科, 教授 (60127876)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Yashitaka  Kanazawa University, Pharmacology, Instructor, 大学院・医学系研究科, 助手 (10236333)
HIGUCHI Yoshihiro  Kanazawa University, Pharmacology, Instructor, 大学院・医学系研究科, 助手 (10019630)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥7,400,000 (Direct Cost: ¥7,400,000)
KeywordsLipoxygenase / Macrophage / Oxidized LDL / LDL receptor-related protein / Cholesterol ester / Translocation / 12 / 15-リポキシゲナーゼ / 受容体 / スカベンジャー受容体
Research Abstract

Lipoxygenase incorporates a molecular oxygen regiospecifically and stereospeciflcally into unsaturated fatty acids. There are four classes of enzymes in mammalian tissues; 5-, 8-, 12-, and 15-lipoxygenases, named by the number indicating oxygenation site of arachidonic acid as a substrate. Among the enzymes, 12-lipoxygenases are widely distributed in various tissues and species, and there are three isoforms: platelet, leukocyte and epidermis types. Since the leukocyte 12-lipoxygenase and 15-lipoxygenase-1 are highly related in their primary structures and enzymological properties, these enzymes are collectively called as 12/15-lipoxygenase. A number of evidences support the role of 12/15-lipoxygenase in LDL oxidation. In order to investigate precise mechanisms of the 12/15-lipoxygenase-mediated LDL oxidation, we established a mouse macrophage-like J774A1 cell line overexpressing porcine leukocyte 12-lipoxygenase. The presence of regio- and stereospeciflcally oxygenated product of cholesteryl linoleate in the LDL indicates that the 12/15-lipoxygenase is responsible for cell-mediated LDL oxidation. We also showed that LDL receptor-related protein (LRP) was required for the enzyme-mediated LDL oxidation by macrophages. Furthermore, cholesterol ester selectively transferred from the LDL particle to the plasma membrane via LRP is oxygenated by 12/15-lipoxygenase translocated to this membrane:

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Kawajiri H, Zhuang D-M, Qiao N, Yoshimoto T, Yamamoto M, et al.: "Expression of arachidonate 12-lipoxygenase in rat tissues : Role of the enzyme in glucagon secretion"J Histochem Cytochem. 48. 1411-1420 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhuang D-M, Kawajiri H, Takahashi Y, Yoshimoto T: "Suppression of prostaglandin E2-mediated c-fos mRNA induction by interleukin-4 in murine macrophages"J Biochem. 127. 451-456 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Xu W, Takahashi Y, Sakashita T, Iwasaki T, Hattori H, et al.: "Low density lipoprotein receptor-related protein is required for macrophage-mediated oxidation of low density lipoprotein by 12/15-lipoxygenase"J Biol Chem. 276. 36454-36459 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kadoyama K, Takahashi Y, Higashida H, Tanabe T, et al.: "Cyclooxygenase-2 stimulates production of amyloid β-peptide in neuroblastoma x glioma hybrid NG108-15 cells"Biochem Biophys Res Commun. 281. 483-490 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshimoto T, Takahashi Y: "Arachidonate 12-lipoxygenases"J Lipid Med and Cell Signal. 168-69. 245-262 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhu H, Takahashi Y, Xu W, Kawajiri H, Murakami T, et al.: "Low density lipoprotein receptor-related protein-mediated membrane translocation of 12/15-lipoxygenase is required of oxidation of low density lipoprotein by macrophages"J Biol Chem. 278. 13350-13355 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 吉本谷博: "基礎生化学実験法(分担執筆)"東京化学同人(日本生化学会編). 338 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawajiri H., Zhuang D.-M., Qiao N., Yoshimoto T., Yamamoto M., Iseki S. and Hamaguchi K.: "Expression of arachidonate 12-lipoxygenase in rat tissues: Role of the enzyme in glucagon secretion"J Histochem Cytochem. 48. 1411-1420 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhuang D.-M., Kawajiri H., Takahashi T. and Yoshimoto T.: "Suppression of prostaglandin E2-mediated c-fos mRNA induction by interleukin-4 in murine macrophages"J Biochem. 127. 451-456 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Xu W., Takahashi Y., Sakashita T., Iwasaki T., Hattori H. and Yoshimoto T.: "Low density lipoprotein receptor-related protein is required for macrophage-mediated oxidation of low density lipoprotein by 12/15-lipoxygenase"J Biol Chem. 276. 36454-36459 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kadoyama K., Takahashi Y., Higashida H., Tanabe T. and Yoshimoto T.: "Cyclooxygenase-2 stimulates production of amyloid β-peptide in neuroblastoma x glioma hybrid NG108-15 ceils"Biochem Biophys Res Commun. 281. 483-490 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshimoto T. and Takahashi Y.: "Arachidonate 12-lipoxygenases (A review)"J Lipid Med and Cell Signal. 68-69. 245-262 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhu H., Takahashi Y., Xu W., Kawajiri H., Murakami T., Yamamoto M., Iseki S., Iwasaki T., Hattori H. and Yoshimoto T.: "Low density lipoprotein receptor-related protein-mediated membrane translocation of 12/15-lipoxygenase is required for oxidation of low density lipoprotein by macrophages"J Biol Chem. 278. 13350-13355 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhu, H., Y.Takahashi, W.Xu, H.Kawajiri, T.Murakami, et al.: "Low density lipoprotein receptor-related protein-mediated membrane translocation of 12/15-lipoxygenase is required for oxidation of low density lipoprotein by macrophages"Journal of Biological Chemistry. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshimoto, T, Y.Takahashi: "Arachidonate 12-lipoxygenases"Prostaglandins and Other Lipid Mediators. 68. 245-262 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi, Y., T.Yoshimoto: "What are the functions of mammalian 8-, 12-, and 15-lipoxygenases?"Research Advances in Cancer. 2. 221-229 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Xu, W., et al.: "Low density lipoprotein receptor-related protein is required for macrophage-mediated oxidation of low density lipoprotein by 12/15-lipoxygenase"J. Biol. Chem.. 276. 36454-36549 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Schewe, T., et al.: "Polyphenols of cocoa : inhibition of mammalian 15-lipoxygenase"Biol. Chem.. 382. 1687-1696 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawajiri,H. et al.: "Expression of arachidonate 12-lipoxygenase in rat tissues"J.Histochem.Cytochem.. 48. 1411-1420 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zhuang,D.-M. et al.: "Suppression of prostaglandin E_2-mediated c-fos mRNA induction by interleukin-4 in murine macrophages"J.Biochem.. 127. 451-456 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉本谷博: "タンパク質化学(第4巻)"野崎光洋,折井豊,指吸俊次(廣川書店). 353 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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