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The mechanism of oxidation of model compounds of apo B protein in LDL by Cu(II) complexes

Research Project

Project/Area Number 10672101
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

UEDA Jun-ichi  National Institute of Radiological Sciences, First Group, Senior Researcher, 第1研究グループ, 研究員 (90160168)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordslinoleic acid / lipid peroxidation / copper / complex / ascorbic acid / fluorescence / 銅イオン / 鉄イオン / 銅錯体 / 脂質過酸化 / 低密度リポ蛋白
Research Abstract

Although it is assumed that the bound copper ion is in redox-active state and capable of producing free radicals initiating the chain reaction, the mechanism of copper-induced peroxidation of LDL is still unclear.
Thus, the mechanism of peroxidation of linoleic acid, which is the most abundant polyunsaturated fatty acid in LDL, by some Cu (II) complexes as model compounds of copper bound to apo B protein of LDL was examined by absorption spectroscopy and HPLC. The absorbance at 234 nm due to the formation of conjugated dienes in the reaction of Cu (II) complexes with linoleic acid acid increased with incubation time, reaching a maximum level, and decreased gradually thereafter. The time to reach the maximal value of absorbance at 234 nm was depended on the redox potential of Cu (II) complexes, suggesting that Cu (II) complexes with a high redox potential could oxidize easily linoleic acid to generate linoleic acid hydroperoxide (LOOH). In addition, the addition of hydrogen peroxide (HィイD22ィエD2OィイD22ィエD2) enhanced the oxidation with incubation time more rapidly than in the absence of HィイD22ィエD2OィイD22ィエD2.
The addition of ascorbic acid to Cu (II) (HGG) suppressed the increase in absorbance at 234 nm, depending on the increase in the concentration of ascorbic acid. Fe (III) EDTA-mediated oxidation of linoleic acid was accelerated by the addition of ascorbic acid. On the other hand, the addition of Trolox (a water soluble derivative of α-tocopherol) to Cu (II) (HGG) suppressed the increase in absorbance at 234 nm. On contrary, Fe (III) EDTA-mediated oxidation of linoleic acid was completely inhibited by the addition of Trolox.
In the presence of acetyl-L-lysine, the reaction of Cu (II) complexes with LOOH led to the formation of fluorescence with excitation maximum at 360 nm and emission maximum at 433 nm.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Jun-ichi Ueda: "Reactive oxygen species generated from the reaction of copper (II) complexes with biological reductants cause DNA strand scission"Archives of Biochemistry and Biophysics. 357. 231-239 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 上田順市: "銅錯体・過酸化水素系による脂質の過酸化と分解の機構解明"磁気共鳴と医学. 9. 79-82 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jun-ichi Ueda: "Oxidation of linoleic acid by copper (II) complexes : effects of ligand"Journal of Inorganic Chemistry. 76. 55-62 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jun-ichi Ueda: "Autoxidation of ascorbic acid catalyzed by the copper (II) bound to L-histidine oligopeptides, (His) iGly and acetyl-(His) iGly (I=9,19, and 29)"Chemical Pharmaceutical Bulletin. 48. (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J. Ueda et al.: "Reactive oxygen species generated from the reaction of copper (II) complexes with biological reductants cuase DNA strand scission"Arch.Biochem.Biophys.. 357. 231-239 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J. Ueda et al.: "Oxidation of linoleic acid by copper (II) complexes : effects of ligand"J.Inorg.Chem.. 76. 55-62 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J. Ueda et al.: "Autoxidation of ascorbic acid catalyzed by the copper (II) bound to L-histidine oligo-peptides, (His) iGly and acetyl-(His)iGly (I=9,19, and 29). Relationship between catalytic activity and coordination mode"Chem.Pham.Bull.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 上田順市: "Oxidation of linoleic acid by copper(II) complexes : effects of ligand"J.Inorg.Chem.. 76. 55-62 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 上田順市: "Reactive Oxygen Species Generated from the Reaction of Copper(II)Complexes with Biological Reductants Cause DNA Strend Seission" Archives of Biochemistry and Biophysics. 357・2. 231-239 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 上田順市: "銅錯体・過酸化水素系による脂質の過酸化と分解の機構解明" 磁気共鳴と医学. 9. 79-82 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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