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Dynamics of nitric oxide (NO) in biological miliue and mechanism of NO-induced injury.

Research Project

Project/Area Number 09470174
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionTokai University

Principal Investigator

NAKAZAWA Hiroe  Tokai University, School of Medicine, Professor, 医学部, 教授 (20110885)

Co-Investigator(Kenkyū-buntansha) ICHIMORI Kouji  Tokai Univ., School of Medicine Assistant Professor, 医学部, 講師 (60184636)
ISHIDA Hideyuki  Tokai Univ., School of Medicine Assitant Professor, 医学部, 講師 (20222424)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsnitric oxide / superoxide / peroxynitrite / NO synthase / cytotoxicity / brain ischemia / endotoxin-shock / nitrotyrosine
Research Abstract

An increasing evidence shows extreamely diverse biological functions of NO.However its dynamics in bIological system is not clealy defined due to its short life and low concentration. Furthermore the mechanism of cytotoxic aspect of NO has not been elucidated.
The purposes of this study were 1) to examine the reaction of NO and superoxide since both react each other at a diffusion-limited rate and form peroxynitrite. All of these are potent cytotoxic molecules. 2) to measure productions of NO, superoxide and peroxynitrite in in vitro system using culture cells and in in vivo system using rats. And 3) to demonstrate the role of peroxynitrite in diseases by measuring nitrotyrosine formation as a footprint of peroxynitrite-induced injury in patients who are suffering from endotoxin shock or from chronic allergic rhinitis.
Results
1) Among these NO synthase (bNOS, iNOS, eNOS) the flux of NO from INOS is the most rapid.
2) The generation of superoxide from NO synthases was successful and the kinetics of electron flow in the NOS were clarified.
3) Nitrotyrosine formation was demonstrated in patients with endotoxin shock or allergic rhinitis.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (65 results)

All Other

All Publications (65 results)

  • [Publications] Ichimori K: "Inhibition of Xanthine oxidase and xanthine dehydrogenase by nitric oxide." J Biol Chem. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Honda K: "Inhaled nitric oxide reduces tyrosine after LPS instillation in Lung Tissue of Rats." Am J Resp Crit Care Med. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa S: "Dynamics of nirotyrosine formation and decay in rat brain during focal ischemia." J Cerebr Blood F Met. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hoshiai M: "Impaired sarcoplasmic reticulim function in lipopolysaccharide-induced myocardial dysfunction." Shock. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Momii H: "Inhibition of adhesion molecules Markedly Ameliorates cytokine-induced sustained myocardial dysfunction in dogs in vivo." J Mol Cell Cardiol. 30. 2637-2650 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishida H: "Application of authenic peroxynitrite to biological materials." Methods Enzymol. 301. 402-409 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zhi Su: "Peroxynitrite is not major mediator of endotherial cell injury by activated neutrophils in vitro." Cardiovasc Res. 39. 485-491 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Adachi T: "Inhibition of nitric oxide synthesis aggravates myocardial ischemia in hemorrhagic shock in constant pressure model." Shock. 9. 204-209 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sato M: "Increased nitric oxide in nasal lavage fluid and nitrotyrosin formation in nasal mucosa --Indices for sever perennial nasal allergy." Clin Exp Allergy. 28. 597-605 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oyama J: "Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo." J Clin Invest. 101. 2207-2214 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukuyama N: "Peroxynitrite formation in focal cerebral ischemia-reperfusion in rat occurs predominantly in the peri-infarct region." J Cereb Blood Flow Metab. 18. 123-129 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuji C: "The importance of polymorphnuclear leukocytes in lipopolysaccharide-induced superoxide anionproduction and lung injury." Lung. 176. 1-13 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukahori M: "Early reperfusion induces alveolar injury in pulmonary embolism." Chest. 111. 198-203 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujii H: "NO inactivates NADPH oxidase in pig neutrophils by inhibiting its assembling process." J Biol Chem. 52. 32773-3278 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka K: "Nitric oxide mediates murine cytomegalovirus-associated pneumonitis in the lungs that are free of the virus." J Clin Invest. 100. 1822-1830 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 源河朝広: "続心臓代謝実験法" 六法出版社, 8 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 星合清隆: "抗酸化物質のすべて" 先端医学社, 7 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishida H: "The Ischemic Heart" Mochizuki S, Takeda N, Nagano M, Dhalla NS, 16 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka Y: "Medical Applications of Synchrotron Radiation" Ando M, Uyama C, 5 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishida H: "Pathophysiology of Lipid Peroxides and Related Radicals" Japan Sci.Soc., 16 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 広田有希: "磁気共鳴と医学9" 日本医学館, 5 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ichimori K: "Inhibition of Xanthine oxidase and xanthine dehydrogenase by nitric oxide." J Biol Chem. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Honda K: "Inhaled nitric oxide reduces tyrosine after LPS instillation in lung tissue of rats." Am J Resp Crit Care Med. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa S: "Dynamics of nirotyrosine formation and decay in rat brain during focal ischemia." J Cerebr Blood F Met. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hoshiai M: "Impaired sarcoplasmic reticulim function in lipopolysaccharide-induced myocardial dysfunction." Shock. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Momii H: "Inhibition of adhesion molecules Markedly Ameliorates cytokine-induced sustained myocardial dysfunction in dogs in vivo." J Mol Cell Cardiol. 30. 2637-2650 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishida H: "Application of authenic peroxynitrite to biological materials." Methods Enzymol. 301. 402-409 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ito K: "A microangiographic technique using synchroton radiation to visualize dermal circulation in vivo." Plastic and Reconstructive Surgery. 102. 1128-1133 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zhi Su: "Peroxynitrite is not major mediator of endotherial cell injury by activated neutrophils in vitro." Cardiovasc Res. 39. 485-491 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Adachi T: "Inhibition of nitric oxide synthesis aggravates myocardial ischemia in hemorrhagic shock in constant pressure model." Shock. 9. 204-209 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sato M: "Increased nitric oxide in nasal lavage fluid and nitrotyrosin formation in nasal mucosa--Indices for sever perennial nasal allergy." Clin Exp Allergy. 28. 597-605 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oyama J: "Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo." J Clin Invest. 101. 2207-2214 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukuyama N: "Peroxynitrite formation in focal cerebral ischemia-reperfusion in rat occurs predominantly in the peri-infarct region." J Cereb Blood Flow Metab. 18. 123-129 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuji C: "The importance of polymorphnuclear leukocytes in lipopolysaccharide-induced superoxide anionproduction and lung injury." Lung. 176. 1-13 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukahori M: "Early reperfusion induces alveolar injury in pulmonary embolism." Chest. 111. 198-203 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujii H: "NO inactivates NADPH oxidase in pig neutrophils by inhibiting its assembling process." J Biol Chem. 52. 32773-3278 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka K: "Nitric oxide mediates murine cytomegalovirus-associated pneumonitis in the lungs that are free of the virus." J Clin Invest. 100. 1822-1830 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishida H: "Pathophysiology of Lipid Peroxides and Related Radicals." Japan Sci. Soc.16 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirota, Y: "Magnetic Resonance in Medicine IX" Nihonigakukan. 4 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Genka C: Method of Cardiac Research II. Roppou Publishers, 8 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hoshiai K: Review in Antioxidants. Sentanigakusha, 7 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishida H: The Ischemic Heart. Mochizuki S,Takeda N,Nagano M,Dhalla NS, 16 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka Y: Medical Applications of Synchrotron Radiation. Ando M,Uyama C, 5 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ichimori K: "Inhibition of Xanthine oxidase and xanthine dehydrogenase by nitric oxide." J Biol Chem. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Honda K: "Inhaled nitric oxide reduces tyrosine after LPS instillation in Lung Tissue of Rats." Am J Resp Crit Care Med. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Takizawa S: "Dynamics of nirotyrosine formation and decay in rat brain during focal ischemia." J Cerebr Blood F Met. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Hoshiai M: "Impaired sarcoplasmic reticulim function in lipopolysaccharide-induced myocardial dysfunction." Shock. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Momii H: "Inhibition of adhesion molecules Markedly Ameliorates cytokine-induced sustained myocardial dysfunction in dogs in vivo." J Mol Cell Cardiol. 30. 2637-2650 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishida H: "Application of authenic peroxynitrite to biological materials." Methods Enzymol. 301. 402-409 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Zhi Su: "Peroxynitrite is not major mediator of endotherial cell injury by activated neutrophils in vitro." Cardiovasc Res. 39. 485-491 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Adachi T: "Inhibition of nitric oxide synthesis aggravates myocardial ischemia in hemorrhagic shock in constant pressure model." Shock. 9. 204-209 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oyama J: "Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo." J Clin Invest. 101. 2207-2214 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 源河朝広: "続心臓代謝実験法" 六法出版社, 8 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 星合清隆: "抗酸化物質のすべて" 先端医学社, 7 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishida H: "Pathophysioiogy of Lipid Peroxides and Related Radicals" Yagi K, 17 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 広田有希: "磁気共鳴と医学9" 日本医学館, (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishida H: "The Ischemic Heart" Mochizuki S,Takeda N,Nagano M,Dhalla NS, 16 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka Y: "Medical Applications of Synchrotron Radiation" Ando M,Uyama C, 5 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sato M,et al.: "Increased nitric oxide in nasal lavage fluid and nitrotyrosin formation in nasal mucosa--Indices for sever perennial nasal allergy." Clinical and Experimental Allergy. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsuji C,et al.: "The importance of polymorphnuclear leukocytes in lipopolysaccharide-induced superoxide anionproduction and lung injury." Lung. in press (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fukahori M,et al: "Early reperfusion induces alveolar injury in pulmonary embolism." Chest. 111. 198-203 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujii H,et al: "NO inactivates NADPH oxidase in pig neutrophils by inhibiting its assembling process." J Biol Chem. 272. 32773-32778 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka K,et al: "Nitric oxide mediates murine cytomegalovirus-associated pneumonitis in the lunfs that are free of the virus." J Clin Invest. 100. 1822-1830 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fukuyama N,et al: "Peroxynitrite formation in rat transient focal ischemia." J Cereb Blood Flow Metab. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishida H,Minhaz U,et al.: "Interaction of Superoxide,Nitric Oxide,and Peroxynitrite under Various Pathological Conditions." Japan Sci.Soc.Press, 12 (1998)

    • Related Report
      1997 Annual Research Report

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

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