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Molecular mechanism on the maturation of tissue oxygen supply system

Research Project

Project/Area Number 15590186
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionKagawa University, Faculty of Medicine

Principal Investigator

KOSAKA Hiroaki  Kagawa University, Faculty of Medicine, Professor, 医学部, 教授 (60158897)

Co-Investigator(Kenkyū-buntansha) IGARASHI Junsuke  Kagawa University, Faculty of Medicine, Associated Professor, 医学部, 助教授 (20346638)
FUJII Shigemoto  Kagawa University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (00325333)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsNitric oxide / NADPH oxidase / ROS / Nitric oxide synthase / Arginine / Sphingosine-1 Phosphate / S1P1 / 血管内皮細胞 / スフィンゴ脂質 / 血管新生 / 内皮型NO合成酵素 / G蛋白質結合型受容体 / 成長因子
Research Abstract

Maturation of tissue oxygen supply system is an important issue to supply oxygen to tissues after tissue injury or vascular obstruction. Sphingosine 1-Phosphate, S1P is a lipid mediator derived from platelets and is supposed to be involved in the angiogenesis and its maturation through its G-protein-coupled S1P1 receptor. We examined whether ROS affects S1P1 receptor expression. The results suggest ROS seems to be involved, however, we must now resolve the induction mechanism. The other studies concerning ROS and pathophysiologic state we did is as follows ; We detected that high salt loading for 4 weeks increased excretion of H_2O_2 in urine of Dahl salt sensitive rats, NADPH-dependent superoxide producing activity in enal cortex, urinary 8-isoprostane and thromboxane B_2 excretion, and decreased plasma NO end products, which were counteracted by L-arginine supplement. We examined an increase in the expressions of NADPH oxidase subunits, gp91phox and p47phox, mRNA abundance with RT-PCR in renal cortex, which was counteracted with oral L-arginine supplement. Western blot revealed that high-salt loading increased gp9lphox protein, which was counteracted by L-arginine supplement both in the total homogenates and in the membrane fractions. High-salt loading powerfully increased p47phox protein, which was distinctly counteracted by L-arginine supplement only in the membrane fractions. These results disclosed that high salt loading causes a deficiency in available L-arginine for NO sythases and induces NADPH oxidase activation in the renal cortex of DS rats, which were counteracted by L-arginine supplement. Superoxide production in the renal cortex of DS rats will accelerate sodium reabsorption and hypertension, since NO inhibits sodium reabsorption in the cortical collecting duct and superoxide rapidly eliminates NO.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (20 results)

All 2004 2003 Other

All Journal Article (14 results) Publications (6 results)

  • [Journal Article] Inhibition of NF-κB activation and iNOS transcription by prolonged exposure to high glucose in the human keratinocyte cell line, HaCaT2004

    • Author(s)
      K.Nakai
    • Journal Title

      Br J Dermatol 150

      Pages: 640-646

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Effects of thiol antioxidant on NADPH Oxidase in hypertensive Dahl Salt-Sensitive Rats2004

    • Author(s)
      L Zhang
    • Journal Title

      Free Radical Biology & Medicine 37

      Pages: 1813-1820

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Inhibition of NF-κB activation and iNOS transcription by prolonged exposure to high glucose in human keratinocyte cell line, HaCaT.2004

    • Author(s)
      K.Nakai, Y.Kubota, H.Kosaka
    • Journal Title

      Br J Dermatol 150

      Pages: 640-646

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Blood flow-dependent changes in intrarenal nitric oxide levels during anesthesia with halothane or sevoflurane.2004

    • Author(s)
      K.Kusudo, K.Ishii, M.Rahman, Y.Aki, A.Miyatake, H.Kosaka, S.Kimura, T.Komatsu, M.Yokoyama, K.Morita, Y.Abe, A.Nishiyama.
    • Journal Title

      Eur.J.Pharmacol. 498

      Pages: 267-273

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of thiol antioxidant on NADPH Oxidase in hypertensive Dahl Salt-Sensitive Rats.2004

    • Author(s)
      L Zhang, S Fujii, J Igarashi, H Kosaka
    • Journal Title

      Free Radical Biology & Medicine 37

      Pages: 1813-1820

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nitric Oxide Synthase Inhibition by N(G)-Nitro-L-Arginine Methyl Ester Retards Vascular Sprouting in Angiogenesis2003

    • Author(s)
      K.Kon
    • Journal Title

      Microvasc Res 65

      Pages: 2-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Induction of LOX-1 and iNOS expressions by ischemia-reperfusion of rat kidney and opposing effect of L-arginine2003

    • Author(s)
      H Kosaka
    • Journal Title

      FASEB J 17

      Pages: 636-643

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Ascorbate enhances iNOS activity by increasing tetrahydrobiopterin in RAW 264.7 cells2003

    • Author(s)
      K Nakai
    • Journal Title

      Free Radical Biology & Medicine 35

      Pages: 929-937

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] L-Arginine reverses p47phox and gp91phox expression induced by high salt in Dahl rats2003

    • Author(s)
      S Fujii
    • Journal Title

      Hypertension 42

      Pages: 1014-1020

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Nitric Oxide Synthase Inhibition by N(G)-Nitro-L-Arginine Methyl Ester Retards Vascular Sprouting in Angiogenesis.2003

    • Author(s)
      K.Kon, S.Fujii, H.Kosaka, T.Fujiwara.
    • Journal Title

      Microvasc Res 65

      Pages: 2-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of high glucose on NOsynthesis in human keratinocyte cell line (HaCaT).2003

    • Author(s)
      K.Nakai, S.Fujii, A.Yamamoto, J.Igarashi, Y.Kubota, H.Kosaka
    • Journal Title

      J.Dermatological Science. 31

      Pages: 211-218

    • NAID

      50000851268

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of LOX-1 and iNOS expressions by ischemia-reperfusion of rat kidney and opposing effect of L-arginine.2003

    • Author(s)
      H Kosaka, H Yoneyama, L Zhang, S Fujii, A Yamamoto, J Igarashi
    • Journal Title

      FASEB J. 17

      Pages: 636-643

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ascorbate enhances iNOS activity by increasing tetrahydrobiopterin in RAW 264.7 cells.2003

    • Author(s)
      K Nakai, M Urushihara, Y Kubota, H Kosaka
    • Journal Title

      Free Radical Biology & Medicine 35

      Pages: 929-937

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] L-Arginine reverses p47phox and gp91phox expression induced by high salt in Dahl rats2003

    • Author(s)
      S Fujii, L Zhang, J Igarashi, H Kosaka
    • Journal Title

      Hypertension 42

      Pages: 1014-1020

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] S Fujii, L Zhang, J Igarashi, H Kosaka: "L-Arginine reverses p47phox and gp91phox expression induced by high salt in Dahl rats."Hypertension. 42. 1014-1020 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Nakai, Y.Kubota, H.Kosaka: "Inhibition of NF-κB activation and iNOS transcription by prolonged exposure to high glucose in human keratinocyte cell line, HaCaT."Br J Dermatol. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] K Nakai, M Urushihara, Y Kubota, H Kosaka: "Ascorbate enhances iNOS activity by increasing tetrahydrobiopterin in RAW 264.7 cells."Free Radical Biology & Medicine. 35. 929-937 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H Kosaka, H Yoneyama, L Zhang, S Fujii, A Yamamoto, J Igarashi: "Induction of LOX-1 and iNOS expressions by ischemia-reperfusion of rat kidney and opposing effect of L-arginine."FASEB J. 17. 636-643 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Nakai, S.Fujii, A.Yamamoto, J.Igarashi, Y.Kubota, H.Kosaka: "Effects of high glucose on NO synthesis in human keratinocyte cell line (HaCaT)."J.Dermatological Science.. 31. 211-218 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Kon, S.Fujii, H.Kosaka, T.Fujiwara: "Nitric Oxide Synthase Inhibition by N(G)-Nitro-L-Arginine Methyl Ester Retards Vascular Sprouting in Angiogenesis."Microvasc Res. 65. 2-8 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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