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Evaluation of antioxidant activity against atherosclerosis using co-culture system

Research Project

Project/Area Number 11672208
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 InstitutionResearch Center for Advanced Science and Technology, University of Tokyo

Principal Investigator

NOGUCHI Noriko  Research Center for Advanced Science and Technology, University of Tokyo, 先端科学技術研究センター, 助手 (40198578)

Co-Investigator(Kenkyū-buntansha) 二木 鋭雄  東京大学, 先端科学技術研究センター, 教授 (20011033)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsCo-culture / Atherosclerosis / Oxidation / LDL / Antioxidants / Cytokine
Research Abstract

To analyze in vitro the migration of monocytes to the subendothelial space, their differentiation into macrophages, and the subsequent formation of form cells in vitro, we developed a 2-coculture system with rabbit aortic endothelial cells, aortic smooth muscle cells, and a mixture of matrix proteins on polyethylene folters in chemotaxis chambers. When oxidized low density lipoprotein (LDL) was added to the matrixlayer of coculture, on day 4 transmigrant cells exhibited lipid deposit droplets, and by day 7, they had the appearance of typical foam cells.
To follow lipid oxidation of low density lipoprotein andwithin cells we developed a novel method using diphenyl-1-pyrenylphosphine (DPPP) as a fluorescent probe. DPPP reacted with organic hydroperoxides and hydrogen peroxide stoichiometrically to give DPPP oxide (DPPP=O). DPPP incorporated into phosphatidylcholine liposomal membranes and polymorphonuclear leukocytes (PMNs) reacted with methyl linoleate hydroperoxide rapidly but not with … More hydrogen peroxide nor with tert-butyl hydroperoxide. This novel method revealed that lipid peroxidation proceeded within membranes of PMN stimulated by phorbol-12-myristate-13-acetate, which is known to produce several kinds of free radicals. It was found that DPPP is a suitable fluorescent probe to monitor lipid peroxidation within the cell membranes specifically. DPPP incorporated into LDL gave a strong fluo-rescence within macrophage after macrophage took up DPPP-containing LDL.
We examined antioxidant activity of 4 isomers of vitamin E, (α- and γ-) tocopherol and tocotrienol, and inhibitory effect on expression of adhesion molecule of human endothelial cell. There were not significant deffereces in antioxidant activity and inhibitory effect on adhesion molecule expression. However, the concentrations of tocotrienols within cell were more than 10 times higher than that of tocopherol due to double bond in side chain of tocotrienol. By taking the defference in the concentrations of these antioxidants into considerations , tocopherols were more efficient in inhibition of the expression of adhesion molecules than tocotrienols. It is interesting to investigate these effects in coculture system we developed. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Noriko Noguchi: "Antioxidant action of antihypertensive drug, carvedilol, against lipid peroxidation"Biochem.Pharmacol.. 59. 1069-1076 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akira Watanabe: "Stability and reactivity of aryloxyl radicals derived from a novel antioxidant BO-653 and related compounds. Effects of substituent and side chain in solution and membranes"J.Am.Chem.Soc.. 122. 5438-5224 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuko Okimoto: "A novel fluorescent probe diphenyl-1-pyrenylphosphine to follow lipid peroxidation in cell membrane"FEBS Letters. 474. 137-140 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noriko Noguchi: "Role of myeloperoxidase in the neutrophil-induced oxidation of low density lipoprotein as studied by myeloperoxidase-knockout mouse"J.Biochem. 127. 971-976 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.H.Kim: "Inhibition of c-Jun expression induces antioxidant enzymes under serum deprivation"Arch.Biochem.Biophys.. 374. 339-346 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wakako Takabe: "Gene expression induced by BO-653, probucol and BHQ in human endothelial cells"J.Atheroscler.Thromb. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honglian Shi: "Methods in Enzymology"ACADEMIC PRESS(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Noguchi, K.Nishino, E.Niki: "Antioxidant action of antihypertensive drug, carvedilol, against lipid peroxidation"Biochem.Pharmacol.. 59. 1069-1076 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Watanabe, N.Noguchi, S.Fujisawa, T.Kodama, K.Tamura, O.Cynshi, E.Nik: "Stability and reactivity of aryloxyl radicals derived from a novel antioxidant BO-653 and related compounds. Effects of substituent and side chain in solution and membranes"J.Am.Chem.Soc.. 122. 5438-5224 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Okimoto, A.Watanabe, E.Niki, T.Yamashita, N.Noguchi: "A novel fluorescent probe diphenyl-1-pyrenylphosphine to follow lipid peroxidation in cell membrane"FEBS Letters. 474. 137-140 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Noguchi, K.Nakano, Y.Aratani, H.Koyama, T.Kodama, E.Niki: "Role of myeloperoxidase in the neutrophil-induced oxidation of low density lipoprotein as studied by myeloperoxidase-knockout mouse"J.Biochem.. 127. 971-976 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] W.Takabe, C.Mataki, Y.Wada, M.Ishii, A Izumi, H.Aburatani, T.Hamakubo, E.Niki, T.Kodama, N.Noguchi: "Gene expression induced by BO-653, probucol and BHQ in human endothelial cells"J.Atheroscler.Thromb.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] W.Takabe, E.Niki, K.Uchida, S.Yamada, T Satoh, N.Noguchi: "Oxidative stress promotes teh development of transformation : involvement of a potent mutagenic lipid peroxidation product, acrolein"Carcinogenesis. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Shi, N.Nouchi, E.Niki: "Methods in Enzymology"Academic Press. 335, (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noriko Noguchi: "Antioxidant action of antihypertensive drug, carvedilol, against lipid peroxidation"Biochem.Pharmacol.. 59. 1069-1076 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akira Watanabe: "Stability and reactivity of aryloxyl radicals derived from a novel antioxidant BO-653 and related compounds. Effects of substituent and side chain in solution and membranes"J.Am.Chem.Soc.. 122. 5438-5224 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yuko Okimoto: "A novel fluorescent probe diphenyl-1-pyrenylphosphine to follow lipid peroxidation in cell membrane"FEBS Letters. 474. 137-140 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Noriko Noguchi: "Role of myeloperoxidase in the neutrophil-induced oxidation of low density lipoprotein as studied by myeloperoxidase-knockout mouse"J. Biochem. 127. 971-976 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.H.Kim: "Inhibition of c-Jun expression induces antioxidant enzymes under serum deprivation"Arch.Biochem.Biophys.. 374. 339-346 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wakako Takabe: "Gene expression induced by BO-653; probucol and BHQ in human endothelial cells"J.Atheroscler.Thromb. (in press). (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Honglian Shi: "Methods in Enzymology"ACADEMIC PRESS (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hiromasa Yamashita: "Oxidation of low density lipoprotein and plasma by 15-lipoxygenase and free radicals"FEBS Lett.. 445. 287-290 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Honglian Shi: "Formation of phospholipid hydroperxides and its ihinibition by a-tocopherol in rat brain synaptosomes induced by peroxynitrite"Biochem. Biophys. Res. Commun.. 257. 651-656 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Noriko Noguchi: "Action of quinolinic and indolinonic aminxyls as radical-scavenging antioxidant"Chem. Phys. Lipids. 99. 11-19 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mikio Takaku: "An In Vitro Coculture Model of Transmigrant Monocytes and Foam Cell Formation"Arterioscler Thromb Vasor. Biol.. 19. 2330-2339 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiromasa Yamashita: "Oxidation of low density lipoprotein and plasma by 15-lipoxygenase and free radicails"FEBS. Lett.. 445. 287-290 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Honglin Shi: "Dynamics of antioxidant action of ubiquinol : a reappraisal"BioFactors. 9. 141-148 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Norimasa Yoshida: "Vitamin E protects against polymorphonuvlear leukocyte-dependent adhesion to endothelial cells"J. Leukocyte Biol.. 65. 757-763 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akira Watanabe: "Rate constants for hydrogen atom abstraction by a-tocopheroxy radical from lipid, hydroperoxide and ascorbic acid"Chem. Lett.. 613-614 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Honglian Shi: "Comparative study on dynamics of antioxidative action of a-tocopheryl hydroquinone, ubiquinol, and a-tocopherol against lipid peroxidation"Free Rad. Biol. Med.. 27. 334-346 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kimihiro Nishino: "Dynamics of action of bisphenol as radical-scavenging antioxidant against lipid peroxidation in solution and liposomal membranes"Free. Rad. Res.. 31. 535-548 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kazuhiro Miyauchi: "Action of pyroloquinolinequinol as an antioxidant againsot lipid peroxidation in solution"Antioxidants Redox Signaling. 1. 547-554 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yon. Hui. Kim: "Tnnibition of c-jun expression induces antioxidant enzymes under serum deprivation"Arch. Biochem. Biophys.. 374. 339-346 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Noriko Noguchi: "Antioxidants in Human Health & Disease"CAB International. 450 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 野口範子: "老化予防食品の開発"シーエムシー. 413 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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