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Viral Pathogenesis and Regulation Mechanism of Free Radicals in Host Responses : Role of Nitric Oxide

Research Project

Project/Area Number 07670347
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionKumamoto University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) NOGUCHI Youichiro  Kumamoto University School of Medicine Instructor, 医学部, 助手 (10244112)
MAEDA Hiroshi  Kumamoto University School of Medicine Professor, 医学部, 教授 (90004613)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsfree radicals / nitric oxide / peroxynitrite / virus infection / influenza virus / herpes simplex virus / viral pathogenesis
Research Abstract

To date, importance of free radical molecular species in the pathogenesis of various viral diseases has been increasingly recognized. Considerable attenstion is given to another type of simple inorganic radical nitric oxide (NO) in the host defense mechanism and pathogenesis of virus infection. It is now well documented that NO synthesis pathway in particular inducible isoform of NO synthase (iNOS) is expressed in different array of virus diseases via induction of proinflammatory cytokines such as interferon-gamma, and interleukin-1beta. Recent studies indicate that NO together with oxygen radicals particularly superoxide (O_2) produced excessively play an important role in inflammatory response of the host against various intruding microbes. A highly reactive nitrogen oxide species peroxynitrite is produced in biological systems through the reaction of NO with O_2. In this research project, role of NO in the pathogenesis of animal models of influenza virus and herpes simplex virus infections was investigated. As a results, we found a convincing evidence that formation of peroxynitrite is critically involved in the pathogenesis of influenza virus infection in mice. Thus, understanding of the role of NO in conjunction with oxygen radicals generated in virus infectionswill provide a new insight into the viral pathogenesis. More importantly, a novel therapeutic approach by regulating the free radical generation may be possible in various viral diseases in humans.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (72 results)

All Other

All Publications (72 results)

  • [Publications] T.Akaike,et al.: "Effect of neurotropic virus infection on neuronal and inducible nitric oxide synthase activity in rat brain" J.Neuro Virology. 1. 118-125 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Aoki,et al.: "Antiviral effect of oryzacystatin,a proteinase inhibitor in rice,against herpes simplex virus type 1 in vitro and in vivo" Antimicrob.Agents Chemother.39. 846-849 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike,et al.: "Determination of peroxyl radical-scavenging activity in food by using bactericidal action of alkyl peroxyl radical" J.Agric.Food Chem.43. 1864-1870 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章: "ウイルス感染病態とNO" 実験医学増刊号「NO研究の最前線」. 13. 1025-1028 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike,et al.: "Pathogenesis of influenza virus-induced pneumonia : Involvement of both nitric oxide and oxygen radicals" Proc.Natl.Acad.Sci.U.S.A.93. 2448-2453 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Miyamoto,et al.: "Potentiation of nitric oxide-mediated vasorelaxation by xanthine oxidase inhibitors" Proc.Soc.Exp.Biol.Med.211. 366-373 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Doi,et al.: "Excessive production of nitric oxide in rat solid tumor and its implication in rapid tumor growth" Cancer. 77. 1598-1604 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Setoguchi,et al.: "Expression of inducible nitric oxide synthase and its involvement in pulmonary granulomatous inflammation in rats" Am.J.Pathol.149. 2005-2022 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.Noda,et al.: "Pharmacological advantages of conjugation of Cu,Zn-superoxide dismutase with succinylated keratin fragment : Improvement of biological properties and resistance to oxidative damage" J.Pharmacol.Exp.Therapeut.279. 162-171 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Maeda,et al.: "Bradykinin and nitric oxide in infectious disease and cancer" Immunopharmacology. 33. 222-230 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike and H.Maeda: "Quantitation of nitric oxide using 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO)" Methods Enzymol.268. 211-221 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章,他: "インフルエンザウイルス肺炎病態への一酸化窒素の関与" THE LUNG-Perspective-. 4. 82-87 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章: "NOと感染防御/炎症反応" 化学療法の領域. 12. 254-259 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章,他: "スーパーオキシドと一酸化窒素の毒性発現機構" 組織培養. 22. 125-131 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章,他: "ウイルス感染とフリーラジカル" 医学のあゆみ. 177. 869-873 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章: "インフルエンザウイルス肺炎病態におけるフリーラジカルの役割" 化学療法の領域. 12. 1811-1816 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章: "酸化的傷害におけるNOの役割" 現代医療. 28. 2085-2090 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Okamoto,et al.: "Activation of human matrix metalloproteinases by various bacterial proteinases" J.Biol.Chem.272. 6059-6066 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Okamoto,et al.: "Activation of human neutrophil procollagenase by nitrogen dioxide and peroxynitrite : A novel mechanism for procollagenase activation involving nitric oxide" Arch.Biochem.Biophys.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike,et al.: "Free radicals in pathogenesis of viral diseases" Proc.Soc.Exp.Biol.Med.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章: "インフルエンザウイルス感染症" 化学療法の領域. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Maeda,et al.: "In Current Topics in Microbiology and Immunology (eds.H.Koprowski and H.Maeda)" Springer-Verlag,Heidelberg,Berlin, 14 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Maeda,et al.: "In SHOCK. From Molecular and Cellular Level to Whole Body (eds.K.Okada and H.Ogata)" Elsevier Sciences B.V.,Amsterdam,The Netherlands, 10 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章,他: "「ショック-その病態と治療 up-to-date」(岡田和夫編)" 医薬ジャーナル社(大阪), 11 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章,他: "「NOラジカルの医学」(大柳善彦編)" (株)羊土社(東京), 12 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章,他: "季刊化学総説NO-化学と生物(日本化学会編)" 学会出版センター(東京), 8 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章: "活性酸素・フリーラジカル研究の新展開-基礎から臨床まで-" 放射線医学総合研究所, 6 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 赤池孝章: "別冊・医学のあゆみ-NOのすべて-(平田結喜緒編)" 医歯薬出版株式会社(東京), 5 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 小坂博昭,他: "座談会形式NOの基礎と臨床(室田誠逸編)" メディカルレビュー社(東京), 30 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: "Effect of neurotropic virus infection on neuronal inducible nitric oxide synthase activity in rat brain." J.Neuro Virology. 1. 118-125 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Aoki, et al.: "Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against herpes simplex virus type 1 in vitro and in vivo." Antimicrob.Agents Chemother. 39. 846-849 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: "Determination of peroxyl radicalscavenging activity in food by using bactericidal action of alkyl peroxyl radical." J.Agric.Food Chem.43. 1864-1870 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Maeda, et al.: "A new nitric oxide scavenger, imidazolineoxyl N-oxide derivative and its effects in pathophysiology and microbiology. In Current Topics in Microbiology and Immunology (eds.H.Koprowski and H.Maeda)" Springer-Verlag, Heidelberg, Berlin. 37-50 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike: "Viral pathogenesis and NO.(in Japanese)" Experimental Medicine (Jikken igaku) Suppl., 「Frontier of NO Research」. 13. 1025-1028 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: "Pathogenesis of influenza virusinduced pneumonia : Involvement of both nitric oxide and oxygen radicals." Proc.Natl.Acad.Sci.USA. 93. 2448-2453 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Miyamoto, et al.: "Potentiation of nitric oxidemediated vasorelaxation by xanthine oxidase inhibitors." Proc.Soc.Exp.Biol.Med.211. 366-373 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Doi, et al.: "Excessive production of nitric oxide in rat solid tumor and its implication in rapid tumor growth." Cancer. 77. 1598-1604 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Setoguchi, et al.: "Expression of inducible nitric oxide synthase and its involvement in pulmonary granulomatous inflammation in rats." Am.J.Pathol.149. 2005-2022 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.Noda, et al.: "Pharmacological advantages of conjugation of Cu, Zn-superoxide dismutase with succinylated keratin fragment : Improvement of biological properties and resistance to oxidative damage." J.Pharmacol.Exp.Therapeut.279. 162-171 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Maeda, et al.: "Bradykinin and nitric oxide in infectious disease and cancer." Immunopharmacology. 33. 222-230 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: "Quantitation of nitric oxide using 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO)." Methods Enzymol.268. 211-221 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: "Involvement of NO in the pathogenesis of influenza virus pneumonia. (in Japanese)" The LUNG-Perspective-. 4. 82-87 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike: "NO in host defense and inflammation. (in Japanese)" Antibiotics & Chemotherapy (Kagakuryohou no ryouiki). 12. 254-259 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: "Cytotoxic mechanism of superoxide and NO.(in Japanese)" The Tissue Culture (Soshiki baiyou). 22. 125-131 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: "Viral infection and free radicals. (in Japanese)" J.Clin.Exp.Med. (Igakuno ayumi). 177. 869-873 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike: "Role of free radicals in influenza virus pneumonia. (in Japanese)" Antibiotics & Chemotherapy (Kagakuryohou no ryouiki). 12. 1811-1816 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike: "Role of NO in oxidative stress. (in Japanese)" Gendai Iryou. 28. 2085-2090 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: "Nitronyl nitroxides as NO scavengers and a novel quantitative assay for NO using liposome-incorporated nitronyl nitroxides. (ed.Jpn.Chem.Soc.) (in Japanese)" Gakkai Syuppan Center. 30. 63-70 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike: "NO and inflammation. -General Aspects of NO- (ed.Y.Hirata) (in Japanese)" J.Clin.Exp.Med.Suppl.83-87 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Okamoto, et al.: "Activation of human matrix metalloproteinases by various bacterial proteinases." J.Biol.Chem.272. 6059-6066 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxide and peroxynitrite : A novel mechanism for procollagenase activation involving nitric oxide." Arch.Biochem.Biophys.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: "Free radicals in pathogenesis of viral diseases." Proc.Soc.Exp.Biol.Med.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike: "Influenza virus infection. (in Japanese)" Antibiotics & Chemotherapy (Kagakuryohou no ryouiki). (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike: "VII.Present and Future of NO research. 4.High sensitive NO measurement. iii) Quantitative detection of NO with nitronylnitroxides. In Proceeding of the 27th NIRS Symposium on New Development for Active Oxygens and Free Radical Research -From Basic Science to Clinical Applications- (eds.T.Ozawa and O.Yukawa) (in Japanese)" National Institute of Radiological Sciences. 230-235 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Maeda, et al.: Septic shock : Prevention by NO-scavenger (PTIO) and by kinin inhibitor. In SHOCK.From Molecular and Cellular Level to Whole Body (eds.K.Okada and H.Ogata). Elsevier Sciences B.V., Amsterdam, The Netherlands, 43-52 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: III-3. Nitric oxide (NO). "Shock : up-to-date of pathogenesis and therapeutics" (ed.K.Okada) (in Japanese). Iyaku Journal Co., Ltd., 156-166 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike, et al.: NO in intection and inflammation. In NO radical and Medicine (ed.Y.Oyanagi) (in Japanese). Youdosha Co., Ltd., 82-93 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Kosaka, et al.: II.Basic aspects of NO.7.NO measurement. In Basic and Clinical Aspects of NO (ed.M.Murota) (in Japanese). Medical Review Co., Ltd., 244-273 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Akaike,et al.: "Pathogenesis of influenza virus-induced pneumonia : Involvement of both nitric oxide and oxygen radicals" Proc.Natl.Acad.Sci.U.S.A.93. 2448-2453 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Miyamoto,et al.: "Potentiation of nitric oxide-mediated vasorelaxation by xanthine oxidase inhibitors" Proc.Soc.Exp.Biol.Med.211. 366-373 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Doi,et al.: "Excessive production of nitric oxide in rat solid tumor and its implication in rapid tumor growth" Cancer. 77. 1598-1604 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Setoguchi,et al.: "Expression of inducible nitric oxide synthase and its involvement in pulmonary granulomatous inflammation in rats" Am.J.Pathol.149. 2005-2022 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] J.Noda,et al.: "Pharmacological advantages of conjugation of Cu, Zn-superoxide dismutase with succinylated keratin fragment : Improvement of biological propertis and resistance to oxidative damage" J.Pharmacol.Exp.Therapeut.279. 162-171 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Maeda,et al.: "Bradykinin and nitric oxide in infectious disease and cancer" Immunopharmacology. 33. 222-230 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Akaike and H.Maeda: "Quantitation of nitric oxide using 2-phenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO)" Methods Enzymol.268. 211-221 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Okamoto, et al.: "Activation of human matrix metalloproteinases by various bacterial proteinases" J.Biol.Chem.272. 6059-6066 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxide and peroxynitrite : A novel mechanism for procollagenase activation involving nitric oxide." Arch.Biochem.Biophys.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Akaike et al.: "Free radicals in pathogenesis of viral diseases" Proc.Soc.Exp.Biol.Med.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Akaike,et al.: "Pathogenesis of influenza virus-induced pneumonia : Involvement of both nitric oxide and oxygen radicals" Proc.Natl.Acad.Sci.U.S.A.96(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Miyamoto,et al.: "Potentiation of nitric oxide-mediated vasorelaxation by xanthine oxidase inhibitors" Proc.Soc.Exp.Biol.Med.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Doi,et al.: "Direct evidence of excessive production of nitric oxide in solid tumor in rats and implication for rapid tumor growth" Cancer Suppl.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Akaike,et al.: "Methods in Enzymology. (ed.L.Packer)" Academic Press,N.Y. (in press), (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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