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ROLE OF OXIDANT STRESS IN THE PROGRESSION OF ATHEROSCLEROSIS AND THE DEVELOPMENT OF A WAY TO REGULATE ITS PROGRESSION

Research Project

Project/Area Number 10670410
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKAGAWA MEDICAL UNIVERSITY (1999)
Osaka University (1998)

Principal Investigator

FUKUNAGA Megumu  KAGAWA MEDICAL UNIVERSITY HOSPITAL, ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (40283775)

Co-Investigator(Kenkyū-buntansha) HORIO Masaru  OSAKA UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (20273633)
SENDA Shoichi  KAGAWA MEDICAL UNIVERSITY HOSPITAL, PROFESSOR, 医学部・附属病院, 教授 (30145049)
KIYOMOTO Hideyasu  KAGAWA MEDICAL UNIVERSITY, ASSISTANT PROFESSOR, 医学部, 助手 (00304585)
ORITA Yoshimasa  KOSHIEN UNIVERSITY, PROFESSOR, 栄養学部, 教授 (70028398)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥3,100,000 (Direct Cost: ¥3,100,000)
KeywordsISOPROSTANE / OXIDANT STRESS / ATHEROSCLEROSIS / INTRACELLULAR SIGNAL TRANSDUCTION / GENE TRANSFER / MYOCARDIAL INFACTION / PTCA / REPERFUSION INJURY
Research Abstract

1) In bovine aortic endothelial cells, 8-iso-PGFィイD22aィエD2, through enhancement of phosphoinositide turnover, stimulated endothelin-1 production and DNA synthesis, the latter of which was partially inhibited by anti endothelin-1 antibody, suggesting an endothelial growth activity of this eicosanoid.
2) Hydrogen peroxide increased 8-iso-PGFィイD22aィエD2, production from cultured rat mesangial cells time- and dose-dependently. This increase was not inhibited by cyclooxygenase inhibitors, such as indomethacin, dexamethazone, varelyl salicylate, or nimesulide, suggesting its producing mechanism independent of cyclooxygenases. Some drugs possessing anti-oxidant action, like vitamin C, vitamin E, sesamine, or probucol, inhibited 8-iso-PGFィイD22aィエD2, production induced by hydrogen peroxide, suggesting the possible application of this system to examine an anti-oxidant action of some drug.
3) The best condition of gene transfer into rat mesangial cells was obtained with 960 μ F at 200V by electroporation method with its efficiency of 2.5% by using Green Fluorescent Protein as an expression marker.
4) In 17 patients who had undertaken direct PTCA performed to treat acute myocardial infarction induced by the occlusion of the proximal portion in the left anterior descending coronary artery, 8-iso-PGF2ィイD22aィエD2 increased by 2.7 fold as an average immediately after the PTCA and gradually decreased to the basal value. This increased lasted longer in those who had undertaken PTCA 12 hours after the onset of their myocardial infarction. In one of them. CPK did not change while 8-iso-PGFィイD22aィエD2 increased markedly immediately after the PTCA. In those who obtained coronary reperfusion only after the PTCA, 8-iso-PGFィイD22aィエD2 increased more greatly and the peak value was inversely correlated to the left ventricular function 3 months after the PTCA, suggesting the role of 8-iso-PGFィイD22aィエD2 in reperfusion-induced myocardial injury.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Fukunaga,M.: "Regulation of MAP-kinase activation by 8-iso-prostaglandinF_<2α> in cultured rat aortic smooth muscle cells"Recent Advancesin Prostaglandin,Thromboxane,and Leukotriene Research. 193-196 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Moriyama,T.: "Increased oxidative products,N-(carboxymethyl)lysine and 8-iso prostaglandinF_<2α> in the kidneys of mice with unilateral ureteral obstruction"J.Am.Soc.Nephrol. 9. 504A (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 橋本一彦: "急性心筋梗塞に対するdirectPTCA後の8-iso-prostaglandinF_<2α>生成"日循誌. 62巻(Suppl.1). 473 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yura,T,: "Free-redical generated F2-isoprostane stimulates cell proliferation and endothelin-1 expression on endothelial cells"Kidney Int.. 56(2). 471-478 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawada,N.: "Increased oxidative stress in mouse kidneys with unilateral obstruction"Kidney Int.. 56(3). 1004-1013 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukunaga,M.: "Mesangial cells can be the source of 8-Iso-ProstaglandinF_<2α>(8-iso-PGF_<2α>)in response to oxidant stress"J.Am.Soc.Nephrol. 10. 468 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 福永 惠: "培養メサンギウム細胞へのGFP遺伝子導入-lipofectin法とelectroporation法の比較"日腎会誌. 41(3). 348-348 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 福永 惠: "ラット培養メサンギウム細胞からのIsoprostane産生機構の解析"日腎会誌. 41(3). 362-362 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Moriyama, T., Kawada, N., Fukunaga, M., Ando, A., Miyata, T., Kurokawa, K. Imai, E., Hori M.: "Increased oxidative products, N-(carboxymethyl) lysine and 8-iso prostaglandin F2ィイD22aィエD2 in the kidneys of mice with unilateral ureteral obstruction."J. Am. Soc. Nephrol.. 9. 504A-504A (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yura, T., Fukunaga, M., Parekh, KR., Nassar, GM., Badr, KF., Montero, A.: "Free-radical generated F2-isoprostane stimulates cell proliferation and endothelin-1 expression on endothelial cells."Kidney Int.. 56-2. 471-478 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawada, N, Moriyama, T, Ando, A, Fukunaga, M, Miyata, T, Kurokawa, K, Imai, E, Hori, M.: "Increased oxidative stress in mouse kidneys with unilateral obstruction."Kidney Int.. 56-3. 1004-1013 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukunaga, M., Senda, S., Hosotani, Y., Hitonmi, H., Hashimoto, M., Kiyomoto, H., Uchida, K., Takahashi, N., Takenaka, M., Imai, E., Orita, Y., Yuasa, S.: "Mesangial cells can be the source of 8-Iso-Prostaglandin FィイD22aィエD2(8-iso-PGFィイD22aィエD2)in response to oxidant stress."J. Am. Soc. Nephrol.. 10. 468A-468A (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukunaga, M., Yura, T., Takahashi, K., and Badr, KF.: "Regulation of MAP-kinase activation by 8-iso-prostaglandin F2ィイD2a2ィエD2 in cultured rat aortic smooth muscle cells. Recent Advances in Prostaglandin, Thromboxane, and Leukotriene Research (Sinzinger, H., Vane, JR., Samuelsson, B., Paoletti, R., Ramwell, PW., and Wong, PY-K. eds.)"Plenum Publishing Corporation, New York, USA. 193-196 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yura,T.: "Free-radical generated F2-isoprostanestimulates cell proliferation and endothelin-1 expression on endothelial cells."KidneyInt.. 56(2). 471-478 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawada,N.: "Increased oxidative stress in mouse kidneys with unilateral obstruction."KidneyInt.. 56(3). 1004-1013 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukunaga,M.: "Mesangial cells can be the source of 8-Iso-ProstaglandinF_<2α>(8-iso-PGF_<2α>)in response to oxidant stress."J.Am.Soc.Nephrol. 10. 468 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 福永 惠: "培養メサンギウム細胞へのGFP遺伝子導入-lipofectin法とelectropporation法の比較"日腎会誌. 41(3). 348 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 福永 惠: "ラット培養メサンギウム細胞からのIsoprostane産生機構の解析"日腎会誌. 41(3). 362 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukunaga,M.: "Regulation of MAP-kinaseactivation by 8-iso-prostaglandinF_2 in cultured rataortic smooth muscle cells." Recent A dvancesin Prostaglandin,Thromboxane.and Leukotriene Research. 193-196 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Moriyama,T: "increasedoxidativeproducts,n-(carboxymethyl)lysine and 8-isoprostaglandinF_2 in the kidneys of mice with unilateral ureteralobstruction" J.Am.Soc.Nephrol. 9. 504 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasuda,T.: "Generation of 8-iso-prostaglandinF_2 from acuteinfarction heart after coronary balloon angioplasty." 2nd International Congresson Coronary Artery Disease抄録集. (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kijima,Y.: "Generation of 8-iso-prostaglandinF_2 from acuteinfarction heart aftercoronary halloon angioplasty" シンポジウム"Potassium Channelsin Cardiovascular Discascsand Cardioprotection"抄録集. (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 橋村一彦: "急性心筋梗塞に対するdirectPTCA後の8-iso-prostaglandinF_2生成" 日循誌. 62巻(Suppl.1). 473 (1998)

    • Related Report
      1998 Annual Research Report

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

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