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Cell biological control of chronic glomerulonephritis -Analysis of signal transduction molecules in pletelets and glomerular cells-

Research Project

Project/Area Number 61570309
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionOsaka University Medical School

Principal Investigator

FUJIWARA Yoshihiro  Department of Medicine, Osaka University Medical School, 医学部, 助手 (60135473)

Co-Investigator(Kenkyū-buntansha) 申 性孝  大阪大学, 医学部附属病院, 医員
ORITA Yoshimasa  Department of Medicine, Osaka University Medical School, 医学部, 助教授 (70028398)
SHIN SungHyo  Osaka University Hospoital
Project Period (FY) 1986 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1987: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsSiqnal transduction mechanism / Phosphoinositide cycle / Inostiol 1,4,5-trisphosphate / Inositol 1,3,4,5-tetrakisphospate / Cultured rat mesangila cell / Angiotensin II / HPLC / イノシトール-1,4,5-トリホスフェイト / アンジオテンシン【II】 / ホスホイノシチド・サイクル
Research Abstract

Angiotensin II ( AII ) causes the contraction and proliferation of msangial cells, both of which are important in etiology and pathophysiology of chronic glomerulonephritis. Recently lines of evidenc have revealed thath the activation of phosphoinositide cycle ( PI cycle ) is a common signal transduction mechanism in the action of Ca-mobilizing hormones including AII. The possibility has been suggested that the modulation of PI metabolism leads to the discovery of new therapy for chronic glomerulonephritis. Unfortunately, the proeviously published methods for the measurement of inositol phosphates ( IPs ), which should provide direct evidence for activated PI cycle, i.e., phospholipase C-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate, had some disadvantages.
In this research project, therefore, we developed the new high performance liquid chromatography ( HPLC ) method, by which we could evaluate AII-induced changes in IPS in cultured rat mesangial cells. The newly develo … More ped HPLC method has enable us to analyze the change in IPs including inositol 1,4,5-trisphosphate ( Ins(1,4,5)P_3 ), inositol 1,3,4-trisphosphate ( Ins(1,3,4)P_3 ), inositol 1,3,4,5-tetrakisphosphate ( Ins(1,3,4,5)P_4 ), inositol pentakisphosphate ( IP_5 ) and inositol hexakisphosphate ( IP_6 ).
When the cells were treated with 10-7 M AII, the increase of Ins(1,4,5)P_3 was very rapid and transient. The increase of Ins(1,3,4,5)P_4 was also rapid and remained increased for up to 60 sec. The increase of Ins(1,3,4)P_4 followed their increases. Inositol monophosphate and inositol bisphosphate also increased within 30 sec and 5 sec, respectively. Neither IP_5 nor IP_6 was increased by AII. AII-induced increase of IP_1, IP_2 and inositol trisphosphate showed dose-dependency and were completely inhibited by saralasin, the competitive inhibitor for AII.
From these results, we suggest that in cultured rat mesangial cells PI cycle including inositol tris- and tetrakisphosphate pathway is the signal transduction mechanism for AII, which may be coupled with the contraction and proliferation ff the cells. Less

Report

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

    (20 results)

All Other

All Publications (20 results)

  • [Publications] 北村栄作: 日本腎臓学会誌. 28. 200-202 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Satoshi Ochi: Biochimica et Biophysica Acta. 927. 100-105 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] SungHyo Shin: Biochemical and Biophysical Research Communication. 142. 70-77 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 申性孝: 日本腎臓学会誌.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Toshiro Takama: Laboratory Invesigation.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] SungHyo Shin: Kidney International.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshimasa Orita;Edited by F.Shimizu;I.Kihara;T,Oite: "Cell Proliferation and Glomerulonephritis." Nishimara Co.,Ltd.Niigata, 174 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshihiro Fujiwara: "Angiotensin II enhances phoshoinositide turnover in glomerular mesangial cells." The 1987 International Congress on membrane and Membrane Processes, 853 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Eisaku kitamura: "Functions and morphology of mesangium. ( in Japanese )" The Japanese Journal of Nephrology. 28. 200-202 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Satoshi Ochi: "Phosphoinositide turnover enhanced by angiotensin II in isolated rat glomeluri." Biochimica et Biphysica Acta. 927. 100-105 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] SungHyo Shin: "Angiotensin II-induced increase in inositol 1,4,5-trisphosphate in cultured art mesangial cells." Biochemical and Biphysical Research Communication. 142. 70-77 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] SungHyo Shin: "Hormonal regulation of nephron functions ( in Japanese )" The Japanese Journal of Nephrology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] SungHyo Shin: "Inositol tris- and tetrakisphosphate pathway in angiotensin II -stimulated cultured rat mesangial cells evidenced by the refined high performance liquid chromatography." Kidney International.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Toshiro Takama: "Growth-stimulating effect of angiotensin II in cultured rat mesangial cells." Laboratory Investigation.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshimasa Orita: Cell Proliferation and Glomerulonephritis.Edited by F. Shimizu, I. Kihara and T. Oite. Nishimura Co., Ltd. Niigata, 174 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshihiro Fujiwara: Angiotensin II enhances phosphoinositide turnover in glomerular mesangial cells.The 1987 International Congress on Membrane and Membrane Processes, 853 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshihiro Fujiwara: Angiotensin II enhances phosphoinositide turnover in glomerular mesangial cells.The 1987 International Congress on Membrane and Membrane Processes, 853 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Satoshi Ochi: Biochim.Biophys.Acta. 927. 100-105 (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] SungHyo Shin: Biochem.Bicphys.Res.Commun.142. 70-77 (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] Yoshimasa Orita Edited by F.Shimizu;I.Kihara;T.Oite: "Cell Proliferation and Glomerulonephritis" Nishimura Co.,Ltd.Niigata, 174 (1986)

    • Related Report
      1986 Annual Research Report

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

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