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2002 Fiscal Year Final Research Report Summary

Research on the role of NO in microbial pathogenesis

Research Project

Project/Area Number 12470065
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionKumamoto University

Principal Investigator

MAEDA Hiroshi  School of Medicine, Professor, 医学部, 教授 (90004613)

Co-Investigator(Kenkyū-buntansha) AKAIKE Takaaki  School of Medicine, Associate Professor, 医学部, 助教授 (20231798)
Project Period (FY) 2000 – 2002
KeywordsNO / PEROXYNITRITE / HOST DEFENSE / MURINE SALMONELLOSIS / APOPTOSIS / ANTI-APOPTOTIC EFFECT / CYTOPROTECTIVE EFFECT / INOS-DEFICIENT MICE
Research Abstract

The importance of free radical molecular species in the pathogenesis of various viral diseases has been increasingly recognized in recent years. Oxygen radicals such as superoxide and hydroxyl radical have been implicated as possible pathogenic molecules in viral disease pathogenesis. Much attention has been given to another simple inorganic radical [nitric oxide (NO)] in me host's defense mechanism and pathogenesis of virus infection. The NO synthesis pathway, in particular the inducible isoform of NO synthase (iNOS), is expressed in different viral diseases via induction of proinflammatory cytokines such as interferon-α and interleukin-1β. iNOS produces an excessive amount of NO for a long time compared with other constitutive isoforms of NOS, i.e., neuronal NOS and endothelial NOS. NO biosynthesis, particularly through expression of an inducible NO synthase (iNOS), occurs in a variety of microbial infections. Our work on murine salmonellosis in iNOS-deficient mice indicated that NO has significant host defense functions in Salmonella infections not only because of its direct antimicrobial effect but also via cytoprotective actions for infected host cells, possibly through its antiapoptotic effect. Reactive nitrogen oxide species such as peroxynitrite are produced in biological systems through the reaction of NO with superoxide. Among these reactive nitrogen species, peroxynitrite and its biological actions are of considerable interest in that peroxynitrite causes oxidation and nitration of amino acid residues of proteins and guanine of DNA, lipid peroxidation, and DNA cleavage. Peroxynitrite thus formed in infectious foci may be a dominant nitrogen oxide species during the host's defense reactions. Thus, understanding of the role of NO and oxygen radical generation in infections will provide insight into not only viral pathogenesis but also the host-pathogen interaction in microbial infections at a molecular level.

  • Research Products

    (68 results)

All Other

All Publications (68 results)

  • [Publications] T.Akaike, et al.: "Viral mutation accelerated by nitric oxide production during infection in vivo"FASEB J.. 14. 1447-1454 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Sawa, et al.: "Tumor-targeting chemotherapy by a xanthine oxidase-polymer conjugate that generates oxygen radicals in tumor tissue"Cancer Res.. 60. 666-671 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Miyamoto, et al.: "Novel functions of human α_1-protease inhibitor after S-nitrosylation : Inhibition of cysteine protease and antibacterial activity"Biochem.Biophys.Res.Commun.. 267. 918-923 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Miyamoto, et al.: "S-Nitrosylated human α_1-protease inhibitor"Biochim.Biophys.Acta. 1477. 90-97 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Sawa, et al.: "Tyrosine nitration by peroxynitrite formed from nitric oxide and superoxide generated by xanthine oxidase"J.Biol.Chem.. 275. 32467-32474 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Akaike: "The mechanisms of biological S-nitrosation and its measurementcells and tissues"Free Rad.Res.. 33. 461-469 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Kanazawa, et al.: "Formation of abasic sites in DNA by t-butyl peroxyl radicals : implication for potent genotoxicity of lipid peroxyl radicals"Cancer Letters. 156. 51-55 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Akaike, et al.: "Nitric oxide and virus infection"Immunology. 101. 300-308 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] E.Akizuki, et al.: "Role of nitric oxide and superoxide in acute cardiac allograft rejection in rats"Proc.Soc.Exp.Biol.Med.. 225. 151-159 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Kuwahara, et al.: "Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production"Infect.Immun.. 68. 4378-4383 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Ikebe, et al.: "Protective effect of S-nitrosylated α_1-protease inhibitor on hepatic ischemia-reperfusion injury"J.Pharmacol.Exp.Ther.. 295. 904-911 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Suga, et al.: "Characteristic elevation of matrixmetalloproteinase activity in idiopathic interstitial pneumonias"Am.J.Respir.Crit.Care Med.. 162. 1949-1956 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Yogo, et al.: "Different vasculoprotective roles of NO synthase isoforms in vascular lesion formation in mice"Arterioscler.Thromb.Vasc.Biol. 20. E96-E100 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Kanazawa, et al.: "Generation of lipid peroxyl radicals from edible oils and their biological activities : A need for consideration for anti-radical components and purification processing"Bio Factors. 13. 187-193 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Akaike: "Free Radical in viral pathogenesis and mutation"Rev.Med.Virol.. 11. 87-101 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Wu, et al.: "Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinases"Jpn.J.Cancer Res.. 92. 439-451 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Okamoto, et al.: "Activation of matrix metalloproteinases by peroxynitrite-induced protein S-glutathiolation via disulfide S-oxide formation"J.Biol.Chem.. 276. 29596-29602 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Satoh, et al.: "Dexamethazone impairs pulmonary defense against Pseudomonas aeruginosa through suppressing iNOS gene expression and peroxynitrite production in mice"Clin.Exp.Immunol.. 126. 266-273 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Miyajima, et al.: "Matrix metalloproteinases induction by pseudomonal virulence factors and inflammatory cytokines in vitro"Microb.Pathog.. 31. 271-281 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Wu, et al.: "Identification of bradykinin receptors in clinical cancer specimens and murine tumor tissues"Int.J.Cancer. 98. 29-35 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Fang, et al.: "Tumor-targeted delivery of PEG-conjugated D-amino acid oxidase for antitumor therapy via enzymatic generation of hydrogen peroxide"Cancer Res.. 62. 3138-3143 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.S.Alam, et al.: "Host defense role of nitric oxide in murine salmonellosis as a function of its antibacterial and aantiapoptotic activities"Infect.Immun.. 70. 3130-3142 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Okamoto, et al.: "S-Nitrosothiols inhibit cytokine-mediated induction of MMP-9 in airway epithelial cells"Am.J.Respir.Cell Mol.Biol.. 27. 463-473 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.K.Sahoo, et al.: "Pegylated zinc protoporphyrin : A water-soluble heme oxygenase inhibitor with tumor-targeting capacity"Bioconjugate Chem.. 13. 1031-1038 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Kanazawa, et al.: "Dietary lipid peroxidation products and DNA damage in colon carcinogenesis"Eur.Lipid Sci.Technol.. 104. 439-447 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Tanaka, et al.: "Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour"Br.J.Cancer. 88. 902-909 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Akaike, et al.: "8-Nitroguanosine formation in viral pneumonia and its implication for pathogenesis"Proc.Natl.Acad.Sci.U.S.A.. 100. 685-690 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Sugiura, et al.: "New method for quantitative assessment of protein nitration in inflammatory airway diseases"Thorax. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Fang, et al.: "In vivo antitumor activity of pegylated zinc protoporphyrin : Targeted inhibition of heme oxygenase in solid tumor"Cancer Res.. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Akaike, et al.: "Nitric Oxide (ed.L.J.Ignarro)"Academic Press, San Diego. 13 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Maeda, et al.: "The Biology of Nitric Oxide Part 7 (eds.S.Moncada, L.Gustafsson, P.Wiklund and E.A.Higgs)"Portland Press Ltd., London. 1 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Akaike, et al.: "The Biology of Nitric Oxide Part 7 (eds.S.Moncada, L.Gustafsson, P.Wiklund and E.A.Higgs)"Portland Press Ltd., London. 1 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Miyamoto, et al.: "The Biology of Nitric Oxide Part 7 (eds.S.Moncada, L.Gustafsson, P.Wiklund and E.A.Higgs)"Portland Press Ltd., London. 1 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Kanazawa, et al.: "Free Radicals in Food. Chemistry, Nutrition, and Health Effects, ACS Symposium Series 807 (eds., Morello, M.J., Shahidi, F., and Ho, C.-T)"American Chemical Society, Washington, DC.. 19 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Akaike, et al.: "Viral mutation accelerated by nitric oxide production during infection in vivo"FASEB J.. 14. 1447-1454 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Sawa, et al.: "Tumor-targeting chemotherapy by a xanthine oxidase-polymer conjugate that generates oxygen radicals in tumor tissue"Cancer Res.. 60. 666-671 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Miyamoto, et al.: "Novel functions of human α_1-protease inhibitor after S-nitrosylation : Inhibition of cysteine protease and antibacterial activity"Biochem. Biophys. Res. Commun.. 267. 918-923 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Miyamoto, et al.: "S-Nitrosylated human α_1-protease inhibitor"Biochim. Biophys. Acta.. 1477. 90-97 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Sawa, et al.: "Tyrosine nitration by peroxynitrite formed from nitric oxide and superoxide generated by xanthine oxidase"J. Biol. Chem.. 275. 32467-32474 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Akaike: "The mechanisms of biological S-nitrosation and its measurementcells and tissues"Free Rad. Res.. 33. 461-469 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Kanazawa, et al.: "Formation of abasic sites in DNA by t-butyl peroxyl radicals : implication for potent genotoxicity of lipid peroxyl radicals"Cancer Letters. 156. 51-55 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Akaike, et al.: "Nitric oxide and virus infection"Immunology. 101. 300-308 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] E. Akizuki, et al.: "Role of nitric oxide and superoxide in acute cardiac allograft rejection in rats"Proc. Soc. Exp. Biol. Med.. 225. 151-159 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Kuwahara, et al.: "Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production"Infect. Immun.. 68. 4378-4383 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Ikebe, et al.: "Protective effect of S-nitrosylated α_1-protease inhibitor on hepatic ischemia-reperfusion injury"J. Pharmacol. Exp. Ther.. 295. 904-911 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Suga, et al.: "Characteristic elevation of matrixmetalloproteinase activity in idiopathic interstitial pneumonias"Am. J. Respir. Crit. Care Med.. 162. 1949-1956 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Yogo, et al.: "Different vasculoprotective roles of NO synthase isoforms in vascular lesion formation in mice"Arterioscler. Thromb. Vase. Biol.. 20. E96-E100 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Kanazawa, et al.: "Generation of lipid peroxyl radicals from edible oils and their biological activities : A need for consideration for anti-radical components and purification processing"Bio Factors. 13. 187-193 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Akaike: "Free Radical in viral pathogenesis and mutation"Rev. Med. Virol.. 11. 87-101 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Wu, et al.: "Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinases"Jpn. J. Cancer Res.. 92. 439-451 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Okamoto, et al.: "Activation of matrix metalloproteinases by peroxynitrite-induced protein S-glutathiolation via disulfide S-oxide formation"J. Biol. Chem.. 276. 29596-29602 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Satoh, et al.: "Dexamethazone impairs pulmonary defense against Pseudomonas aeruginosa through suppressing iNOS gene expression and peroxynitrite production in mice"Clin. Exp. Immunol.. 126. 266-273 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Miyajima, et al.: "Matrix metalloproteinases induction by pseudomonal virulence factors and inflammatory cytokines in vitro"Microb. Pathog.. 31. 271-281 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Wu, et al.: "Identification of bradykinin receptors in clinical cancer specimens and murine tumor tissues"Int. J. Cancer. 98. 29-35 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Fang, et al.: "Tumor-targeted delivery of PEG-conjugated D-amino acid oxidase for antitumor therapy via enzymatic generation of hydrogen peroxide"Cancer Res.. 62. 3138-3143 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. S. Alam, et al.: "Host defense role of nitric oxide in murine salmonellosis as a function of its antibacterial and antiapoptotic activities"Infect. Immun.. 70. 3130-3142 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Okamoto, et al.: "S-Nitrosothiols inhibit cytokine-mediated induction of MMP-9 in airway epithelial cells"Am. J. Respir. Cell Mol. Biol.. 27. 463-473 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. K. Sahoo, et al.: "Pegylated zinc protoporphyrin : A water-soluble heme oxygenase inhibitor with tumor-targeting capacity"Bioconjugate Chem.. 13. 1031-1038 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Kanazawa, et al.: "Dietary lipid peroxidation products and DNA damage in colon carcinogenesis"Eur. Lipid Sci. Technol.. 104. 439-447 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Tanaka, et al.: "Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour"Br. J. Cancer. 88. 902-909 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Akaike, et al.: "8-Nitroguanosine formation in viral pneumonia and its implication for pathogenesis"Proc. Natl. Acad. Sci. U.S.A.. 100. 685-690 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Sugiura, et al.: "New method for quantitative assessment of protein nitration in inflammatory airway diseases"Thorax. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Fang, et al.: "In vivo antitumor activity of pegylated zinc protoporphyrin : Targeted inhibition of heme oxygenase in solid tumor"Cancer Res.. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Akaike, et al., (ed. L. J. Ignarro): "Nitric Oxide"Academic Press. 13 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Maeda, et al., (eds. S. Moncada, L. Gustafsson, P. Wiklund and E. A. Higgs): "The Biology of Nitric Oxide Part 7"Portland Press Ltd.. 1 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Akaike, et al., (eds. S. Moncada, L. Gustafsson, P. Wiklund and E. A. Higgs): "The Biology of Nitric Oxide Part 7"Portland Press Ltd.. 1 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Miyamoto, et al., (eds. S. Moncada, L. Gustafsson, P. Wiklund and E. A. Higgs): "The Biology of Nitric Oxide Part 7"Portland Press Ltd.. 1 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Kanazawa, et al. (eds., Morello, M. J., Shahidi, F., and Ho, C.-T): "Free Radicals in Food. Chemistry, Nutrition, and Health Effects, ACS Symposium Series 807"American Chemical Society. 19 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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