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Mechanism of the production of reactive nitrogen species during renal ischemic-reperfusion insult

Research Project

Project/Area Number 13670087
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionThe University of Tokushima

Principal Investigator

TAMAKI Toshiaki  The university of Tokushima School of Medicine Professor, 医学部, 教授 (80179879)

Co-Investigator(Kenkyū-buntansha) TSUCHIYA Koichiro  The university of Tokushima School of Medicine Lecturer, 医学部, 助手 (70301314)
YOSHIZUMI Masanori  The university of Tokushima School of Medicine Assistant Professor, 医学部, 講師 (60294667)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsNitric oxide / HbNO / electron paramagnetic resonance / ACE inhibitor / subtraction method / ischemia-reperfused kidney / ^<15>NO_2 / Nitrite / Nitrotyrosine / Electron paramagnetic reson / L-tyrosine / Tyrosine radical / Peroxynitrite
Research Abstract

In circulation, nitric oxide(NO) exists as relatively atable hemoglobin-NO adduct(HbNO), which means that the amount of HbNO may reflect the blood NO concentration. HbNO signal has been reported to be successfully detected in human blood using electron paramagnetic resonance(EPR) method. However, there were some difficulties to obtain a fine HbNO signal of nornal blood. We itroduced the EPR signal subtraction method to overcome the difficulties. Using this method, we confirmed that HbNO concentrarion in pentobarbital-anesthetized rats were augmented by infusion of L-arginine but not D-argimine. We also emenstrated that temocapril, an ACE inhibitor, improved abnormalities of NO dynamics in the L-MAME-induced hypertensive rats.
After the intravebous infusion of ^<15>NO_2, the left renal artery of a rat was clumped for 40 minutes. Five minutes after the release of left renal occluaion, left and right renal tissues and venous blood were obtained. Hb^<15>NO concentration of renal tissues and venous blood was evaluated using EPR method. Hb^<15>NO concentrarion of left (ischemic) renal tissue is much higher than that of right(non-ischemic) renal tissue. Hb^<15>NO concentration of venous blood in ischemic-reperfused rat is much higher than that in aham operated non-ischemic rat. These results indicate that there is NO generation pathway from NO_2 and ischemic-reperfusion insult stimulates the NO generation from NO_2

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] K.Kirima: "Electron paramagnetic resonance study on free radical scavanging and/or generating activity of dopamine-4-0-sulfate"Chemical Pharmaceutical Bulletin. 49. 576-580 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Kagami: "Requirement for tyrosine kinase-ERK1/2 signaling in α1β1 integrin-mediated collagen matrix remodeling by rat mesangial cells"Experimental Cell Research. 268. 274-283 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Yoshizumi: "Quercetin inhibits Shc-and Phosphatidylinositol 3-kinase-mediated c-Jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells"Molecular Pharmacology. 60. 656-665 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Suzaki: "Hydrogen peroxide stimulates c-Src-mediated big mitogem-activated protein kinase 1 (BMK1) and the MEF2C signaling pathway in PC12 cells. Potential role in cell survival following oxidative insults"J.Biol.Chem.. 277. 9614-9621 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Yoshizumi: "Ebselen attenuates oxidative styress-induced apoptosis via the inhibition of the c jun N-terminal kinase and activator protein-I signaling pathway in PC12 cells"Br.J.Pharmacology. 136. 1023-1032 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Tsuchiya: "The role of thiol and nitrosothiol compounds in the nitric oxide-forming reactions of the iron-N-methyl-D-glucamine dithiocarbamate complex"Biochemical Journal. 367. 771-779 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Kirima, K.Tsuchiya, M.Yoshizumi, T.Kameda, H.Houchi, N.Azuma, T.Tamaki: "Electron paramagnetic resonance study on free radical acavanging and/or generating activity of dopamine-4-0-sulfate"Chemical Pharmaceutical. Bulletin 49. 576-580 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Kagami, K.Urushihara, S.Kondo, K.Loster, W.Reutter, T.Tamaki, M.Yoshizumi, Y.Kuroda: "Requirement for tyrosine kinase-ERK1/2 signaling in α1β1 integrin-mediated collagen matrix remodeling by rat mesangial cells"Experimental Cell Research. 268. 274-283 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Yoshizumi, K.Tsuchiya, K.Kirima, Moe.Kyaw, Y.Suzaki, T.Tamaki: "Quercetin inhibits She and Phosphatidylinositol 3-kinase-mediated c-Jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells"Molecular Pharmacology. 60. 656-665 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Suzaki, M.Yoshizumi, S.Kagami, AH.Koyama, Y.Taketani, H.Houchi, K.Tsuchiya, E.Takeda, T.Tamaki: "Hydrogen peroxide stimulatoes c-Src-mediated big mitogen-activated protein kinase 1 (BMK1) and the MEF2C signaling pathway in PC12 cells. Potential role in cell survival following oxidative insults."J.Biol.Chem. 277. 9614-9621 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Urueshihara, S.Kagami, T.Kuhara, T.Tamaki, Y.Kuroda: "Glomerular distribution and gelatinolytic activity of natrix metalloproteinases in human glomerulonephritis"Nephrology Dialysis Transplantation. 17. 1189-1196 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Moe Kyaw, M.Yoshizumi, K.Tsuchiya, K.Kirima, Y.Suzaki, S.Abe, T.Hasegawa, T.Tamaki: "Antioxidants inhibit endothelin-1(1-31)-induced prohferation of vascular smooth muscle cells via the inhibition of mitogen-activated protein (MAP) kinase and activator protein-1(AP-1)"Biochemical Pharmacology. 64. 1521-1531 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Yoshizumi, K.Tsuchiya, Y.Suzaki, K. Kirime, Moe Kyaw, JH.Moon, J.Terao, T.Tamaki: "Quercetin Glucromide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway"Biochemical and Biophysical Research Communications. 293. 1458-1465 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Yoshizumi, T.Kogane, Y.Suzaki, K.Kirima, Moe Kyaw, K.Kirima, K.Ishizawa, K.Tsuchiya, S.Kagami, T.Tamaki: "Ebeelen attenuates oxidative styress-induced apoptosis via the inhibition of the c jun N-terminal kinase and activator protein-1 signaling pathway in PC12 cells"Br.J.Pharmacology. 136. 1023-1132 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Tsuchiya, K.Kirima, M.Yoshizumi, H.Houchi, T.Tamaki, RP.Mason: "The role of thiol and nitrosothiol compounds in the nitric oxide-forming reactions of the iron-N-methyl-D-glucamine dithiocarbamate complex"Biochemical Journal. 367. 771-779 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koichiro Tsuchiya: "The role of thiol and nitrosothiol compounds in the nitric oxide-forming reactions of the iron-N-methyl-D-glucamine dithiocarbamate complex"Biochemical Journal. 367. 771-779 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 土屋浩一郎: "亜硝酸と一酸化窒素(NO)"血管. 25. 63-71 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maki Urushihara: "Glomerular distribution and gelatinolytic activity of natrix metalloproteinases in human glomerulonephritis"Nephrology Dialysis Transplantation. 17. 1189-1196 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shoji Kagami: "Requirement for tyrosine kinase-ERK/2 signaling in a1b1 integrin mediated collagen matrix remodeling by rat mesangial cells"Experimental Cell Research. 268. 274-283 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazuyoshi Kirima: "Electron paramagnetic resonance study on free radical scavanging and/or generating activity of dopamine-4-0-sulfate"Chemical Pharmaceutical Bulletin. 49. 744-750 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuki Suzaki: "Hydrogen peroxide stimulates c-Src-mediated big mitogen-activated protein kinase 1(BMK1)and the MEF2C signaling pathway in PC12 cells"J.Biol.Chem. (in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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