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The clinical analysis of the pathophysiological significance in the kidney disease of the new bioactivation molecule.

Research Project

Project/Area Number 11671056
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTokyo Women's Medical College

Principal Investigator

SHIRAGA Hiroshi  Tokyo Women's Medical College Dept. of Pediatric Nephrology, School of Medicine, 医学部, 助教授 (60175396)

Co-Investigator(Kenkyū-buntansha) AKIOKA Yuko  Tokyo Women's Medical College Dept. of Pediatric Nephrology, School of Medicine Instructor, 医学部, 助手 (90212422)
YOSHIOKA Toshomasa  Tokyo Women's Medical College Dept. of Pediatric Nephrology, School of Medicine Associate Professor, 医学部, 助教授 (60146438)
ITO Katumi  Tokyo Women's Medical College Dept. of Pediatric Nephrology, School of Medicine Professor, 医学部, 教授 (90056771)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsCarvedilol / Endothelial cell line / Toxicity / Electron paramagnetic resonance / NO donor / Fluorescence / Nitric oxide / DAF-2DA / ステロイド依存性 / グルココルチコイド抵抗性 / SSCP法 / グルココルチコイド受容体
Research Abstract

Carvedilol, an adrenoceptor blocker with antioxidant activity, was studied for its ability to interact with Nitric oxide (NO) in a cell-free condition and in an endothelial cell line (ECV304).
In a cell-free system, carvedilol attenuated NO-dependent reduction of carboxy-2-phenyl-4, 4, 5, 5-tetramethyl-imidazoline-1-oxyl-3-oxide induced by a NO donor, (±)-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexenamide, which was determined by electron paramagnetic resonance (EPR) spectrometry. The EPR study also showed that nitrosylhemoglobin formation in rat red blood cells by the addition of NO-saturated solution was attenuated by prior incubation with 0.1 to 10 μM carvedilol. NO-induced fluorescence in 4, 5-diaminofluorescein-2 diacethyl (DAF-2DA)-loaded ECV304 cells was attenuated by carvedilol but not by labetalol. The IC50 of carvedilol for NO donor (1-hydroxy-2-oxo-3-(aminopropyl)-3-isopropyl-1-triazene or sodium nitroprusside)-induced fluorescence of DAF-2DA in ECV304 cells was 【approximately equal】1.0 x10^<-7> M, which was similar to the reported IC50 of carvedilol for the antioxidant effect.
Cell toxicity induced by a NO donor determined by the number of viable cells after 24 hour treatment with 2-2' (hydroxynitrosohydrazino) bis-ethanamine was significantly attenuated by pretreatment with 1 μM carvedilol. Both free and cell-associated carvedilol quenched NO.Because NO mediates both physiological and pathophysiological processes, NO quenching by the drug may have diverse clinical implications depending upon specific functions of local NO in tissues where carvedilol is distributed.

Report

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

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Yoshioka T, et.al.: "Anti-NO action of calvedirol in cell-free system and in vascular endotherial cells."Br.J.Pharmacol.. 129. 1530-1535 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Shiraga,K.Ito, et.al: "A peculiar vacuolization in the kidney transplant of a child treated with tacrolim us."Clin.Transplant.. 14(3). 30-32 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Iwamoto,H.Shiraga,K.Ito, et.al.: "Acetyl-seryl-spartyl-lysyl-proline is a novel natural cell cycle regulator of renal cells"Life Sciences. 66(15). PL221-226 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Yoshioka, et al.: "Association of TGF-b signaling in angiotensin II-induced PAI-1 mRNA upregulation in mesangial cells : role of PKC."Biochemica et Biophysica Acta. 1449. 217-226 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 吉岡俊正: "融合遺伝子発現系による蛋白質可視化技術の分子薬理学的応用"日本薬理学会雑誌. 226. 36-42 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshioka T, et.al.: "Morecular and function characterization of HSC54, a novel variant of human heat-shock congnate protein70"Molecular Pharmacology. 58. 1257-1263 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 白髪宏司,伊藤克己: "Annual Review腎臓2000 肝・腎同時移植"長澤俊彦,伊藤克己,浅野泰,遠藤仁,東原英二 編 中外医薬社. 8 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Iwamoto, H-J.Xiao, T.Yoshioka, H.Shiraga, K.Nitta, T.Muraki, and K.Ito.: "AcSDKP AS A NEW MEDIATOR OF RENAL CELL PROLIFERATION AND A TARGET FOR THE MOLECULAR ACTION OF ACEI."Life Sciences. 66(15). 221-226 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Shiraga, K.Ito, et al.: "A peculiar vacuolization in the kidney transplant of a child treated with tacrolimus."Clin. Transplant. 14. 30-32 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Motojima, J.Kakuchi, T.Yoshioka: "Association of TGF-b signaling in angiotensin II-induced PAD-1 mRNA upregulation in mesangial cells : role of PKC."Biochemica et Biophysica Acta. 1449. 217-226 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshioka T, et.al.: "Anti-NO action of calvedirol in cell-free system and in vascular endotherial cells."Br.J.Pharmacol.. 129. 1530-1535 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Shiraga,K.Ito, et.al.: "A peculiar vacuolization in the kidney transplant of a child treated with tacrolimus."Clin.Transplant.. 14(3). 30-32 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Iwamoto,H.Shiraga,K.Ito, et.al.: "A cetyl-seryl-spartyl-lysyl-proline is a novel natural cell cycle regulator of renal cells."Life Sciences. 66(15). PL221-226 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉岡俊正: "融合遺伝子発現系による蛋白質可視化技術の分子薬理学的応用"日本薬理学会雑誌. 226. 36-42 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉岡俊正: "一酸化窒素および構成型熟ショックタンパク質70によるグルココルチコイド作用の修飾機構の解析"臨床薬理. 31. 331-332 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshioka T, et.al.: "Morecular and function characterization of HSC54, a novel variant of human heat-shock congnate protein 70"Molecular Pharmacology. 58. 1257-1263 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 白髪宏司,伊藤克己: "Annual Review腎臓2000 肝・腎同時移植"長澤俊彦,伊藤克己,浅野泰,遠藤仁,東原英二 編 中外医薬社. 8 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toshimasa Yoshioka,et al.: "Association of TGF-β signaling in angiotensin II-induced PAI-1 mRNA upregulation in mesangeal cells ; role of PKC"Biochemica et Miophysicia Acta. 1449. 217-226 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N,Iwamoto,T,Yoshioka,H,Shiraga,K,Ito,et al.: "Acetyl-Setyl-Asparatyl-Proline is a novel natural cell cycle regulator of renal cells"Life Sciences. 66(15). 221-226 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 白髪宏司,伊藤克己他: "透析治療の進歩"日本小児腎不全学会雑誌. 19. 1-3 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 白髪宏司,伊藤克己他: "小児嚢性腎疾患の移植医療"日本小児腎不全学会雑誌. 19. 64-66 (1999)

    • Related Report
      1999 Annual Research Report

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

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