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2002 Fiscal Year Final Research Report Summary

Research on microbial mutation and evolution involving oxidative stress

Research Project

Project/Area Number 12470038
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKumamoto University

Principal Investigator

AKAIKE Takaaki  School of Medicine, Associate Professor, 医学部, 助教授 (20231798)

Co-Investigator(Kenkyū-buntansha) MAEDA Hiroshi  School of Medicine, Professor, 医学部, 教授 (90004613)
Project Period (FY) 2000 – 2002
KeywordsOXIDATIVE STRESS / GENETIC MUTATION / MUTAGENESIS / VIRAL MUTATION / MOLECULAR EVOLUTION / NO / 8-MTROGUANOSINE / NITRATIVE STRESS
Research Abstract

Oxygen radicals and nitric oxide (NO) are generated in excess in a diverse array of microbial infections. Emerging concepts in free radical biology are now shedding light on the pathogenesis of various diseases. Free-radical induced pathogenicity in virus infections is of great importance, because evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases. Although oxygen radicals and NO have an antimicrobial effect on bacteria and protozoa, they have opposing effects in virus infections such as influenza virus pneumonia and several other neurotropic virus infections. A high output of NO from inducible NO synthase, occurring in a variety of virus infections, produces highly reactive nitrogen oxide species, such as peroxynitrite, via interaction with oxygen radicals and reactive oxygen intermediates. The production of these various reactive species confers the diverse biological functions of NO. The reactive nitrogen species cause oxidative tissue injury and mutagenesis through oxidation and nitration of various biomolecules such as guanosine. The unique biological properties of free radicals are further illustrated by recent evidence showing accelerated viral mutation by NO-induced oxidative stress. NO appears to affect a host's immune response, with immunopathological consequences. For example, NO is reported to suppress type 1 helper T cell-dependent immune responses during infections, leading to type 2 helper T cell-biased immunological host responses. NO-induced immunosuppression may thus contribute to pathogenesis of virus infections and help expansion of quacispeies population of viral pathogens. In the present study, we indeed successfully elucidated the critical roles of NO in the pathogenesis of viral diseases and in viral mutation as related to nucleic acid modifications by NO, i.e., nitration of guanosine to form 8-nitroguanosine.

  • Research Products

    (66 results)

All Other

All Publications (66 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.Saws, 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 disulfideS-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] 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 antiapoptotic 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] T.Sawa, 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.: "Viral mutation accelerated by nitric oxide production during infection in vivo"FASEB J.. 14. 1447-1450 (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 measureinentcells 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. Kuwahra, et al.: "Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production"Infect Inmun.. 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-nitrosylaetd 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] 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. L 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 LJ. 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] T. Sawa, 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

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Published: 2004-04-14  

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