1997 Fiscal Year Annual Research Report

ウイルス感染におけるフリーラジカルの分子病態とそのレドックス制御についての研究

Research Project

Project/Area Number	09470046
Research Institution	Kumamoto University
Principal Investigator	赤池孝章熊本大学, 医学部, 助教授 (20231798)
Co-Investigator(Kenkyū-buntansha)	澤智裕熊本大学, 医学部, 助手 (30284756) 前田浩熊本大学, 医学部, 教授 (90004613)
Keywords	フリーラジカル / NO / 病原因子 / ウイルス感染病態 / NO消去剤
Research Abstract	ウイルス感染病態におけるフリーラジカルの役割を明らかにするため、インフルエンザウイルス肺炎モデル、ラット単純ヘルペスウイルス1型(HSV-1)脳炎モデルおよびマウスコクサッキーウイルス心筋炎モデルを用いて、一酸化炭素(NO)の産生動態と、その病態生理活性について検討した。その結果、既に報告したインフルエンザ感染病態のみならず、HSV-1脳炎モデルにおいて、ウイルス感染脳病巣において誘導型NO合成酵素(iNOS)の発現と、本酵素によるNOの過剰生成がもたらされることがわかった。また、本モデルにNOS阻害剤(N^ω-monomethyl-L-arginine)を投与することにより、宿主の抗ウイルス防御能を損なうことなく、脳炎病態が著明に改善することが明らかになった。同様に、コクサッキーウイルス心筋炎においても、過剰に生成するNOが、重要な病原因子であることを我々の開発したNO消去剤リポソームPTIOを用いて証明することができた。あわせて、本年度は、ウイルス感染病態で過剰に産生されるパーオキシナイトライト(ONOO^-)の病原性発現メカニズムを解析したところ、パーオキシナイトライトが、宿主のマトリックスメタロプロテアーゼを活性化し感染病巣における組織障害を増悪させる可能性が示唆された。また大変興味あることに、パーオキシナイトライトの消去剤として知られるエブセレンがインフルエンザウイルス肺炎病態を改善させることも明らかとなった。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] T. Okamoto, et al.: "Activation of human matrix metalloproteinases by various bacterial proteinases" J. Biol. Chem.272. 6059-6066 (1997)
[Publications] H. Muranaka, et al.: "Superoxide scavenging activity of erythromycin-iron complex" Biochem. Biophys. Res. Commun.232. 183-187 (1997)
[Publications] D.C. Hooper, et al.: "Prevention of experimental allergic encephalitis by targeting nitric oxide and peroxynitrite : Implications for the treatment of multiple sclerosis" Proc. Natl. Acad. Scie. U.S.A. 94. 2528-2533 (1997)
[Publications] K. Umezawa, et al.: "Induction of nitric oxide synthesis and xanthine oxidase and their role in the antimicrobial mechanism against Salmonella typhimurium in mice" Infect. Immun.65. 2932-2940 (1997)
[Publications] T. Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxides and peroxynitrite : A novel mechanism for procollagenase activation involving nitric oxide" Arch. Biochem. Biophys.342. 261-274 (1997)
[Publications] T. Akaike, et al.: "Nanomolar quantification and identification of various nitrosothiols by high performance liquid chromatography coupled with flow reactors of metals and Griess reagent" J. Biochem.122. 459-466 (1997)
[Publications] K. Kojima, et al.: "Development of a fluorescent indicator for bioimaging of nitric oxide" Biol. Pharm. Bull.20. 1229-1232 (1997)
[Publications] K. Sato, et al.: "Nitric oxide generation from hydroxyurea via copper-catalyzed peroxidation and implications for pharmacological actions of hydroxyurea" Jpn. J. Cancer Res.88. 1199-1204 (1997)
[Publications] T. Akaike, et al.: "Free radicals in viral pathogenesis : Molecular mechanisms involving superoxide and NO" Proc. Soc. Exp. Biol. Med.217. 64-73 (1997)
[Publications] M. Yoshida, et al.: "Effect of the NO scavenger carboxy-PTIO on endothelium-dependent vasorelaxation of various blood vassels from rabbits" Life Sciences. 62. 203-211 (1998)
[Publications] H. Maeda, et al.: "Human matrix metalloprotease activation by insults of bacterial infection involving proteases and free radicals" Biol. Chem.379. 193-200 (1998)
[Publications] J. Wu, et al.: "Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger" Cancer Res.58. 159-165 (1998)
[Publications] K. Sato, et al.: "Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice." Am. J. Respir. Crit. Care Med.(in press). (1998)
[Publications] H. Maeda, and T. Akaike: "Nitric oxide and oxygen radicals in infection, inflammation and cancer" Biochemistry (Moscow). (in press). (1998)
[Publications] H. Maeda and T. Akaike: "Nitric Oxiden in Transplant Rejection and Anti-tumor Defense (eds. J.L. Zweier and S.J. Lukiewicz)" Kluwer Academic Publishers, Norwell (in press), (1998)
[Publications] T. Akaike and H. Maeda: "Nitric Oxide and Infection (ed. F.C. Fang)" Plenum Publishing Co., New York (in press), (1998)

1997 Fiscal Year Annual Research Report

ウイルス感染におけるフリーラジカルの分子病態とそのレドックス制御についての研究

Principal Investigator

赤池 孝章 熊本大学, 医学部, 助教授 (20231798)

Research Products

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

[Publications] H. Muranaka, et al.: "Superoxide scavenging activity of erythromycin-iron complex" Biochem. Biophys. Res. Commun.232. 183-187 (1997)

[Publications] D.C. Hooper, et al.: "Prevention of experimental allergic encephalitis by targeting nitric oxide and peroxynitrite : Implications for the treatment of multiple sclerosis" Proc. Natl. Acad. Scie. U.S.A. 94. 2528-2533 (1997)

[Publications] K. Umezawa, et al.: "Induction of nitric oxide synthesis and xanthine oxidase and their role in the antimicrobial mechanism against Salmonella typhimurium in mice" Infect. Immun.65. 2932-2940 (1997)

[Publications] T. Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxides and peroxynitrite : A novel mechanism for procollagenase activation involving nitric oxide" Arch. Biochem. Biophys.342. 261-274 (1997)

[Publications] T. Akaike, et al.: "Nanomolar quantification and identification of various nitrosothiols by high performance liquid chromatography coupled with flow reactors of metals and Griess reagent" J. Biochem.122. 459-466 (1997)

[Publications] K. Kojima, et al.: "Development of a fluorescent indicator for bioimaging of nitric oxide" Biol. Pharm. Bull.20. 1229-1232 (1997)

[Publications] K. Sato, et al.: "Nitric oxide generation from hydroxyurea via copper-catalyzed peroxidation and implications for pharmacological actions of hydroxyurea" Jpn. J. Cancer Res.88. 1199-1204 (1997)

[Publications] T. Akaike, et al.: "Free radicals in viral pathogenesis : Molecular mechanisms involving superoxide and NO" Proc. Soc. Exp. Biol. Med.217. 64-73 (1997)

[Publications] M. Yoshida, et al.: "Effect of the NO scavenger carboxy-PTIO on endothelium-dependent vasorelaxation of various blood vassels from rabbits" Life Sciences. 62. 203-211 (1998)

[Publications] H. Maeda, et al.: "Human matrix metalloprotease activation by insults of bacterial infection involving proteases and free radicals" Biol. Chem.379. 193-200 (1998)

[Publications] J. Wu, et al.: "Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger" Cancer Res.58. 159-165 (1998)

[Publications] K. Sato, et al.: "Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice." Am. J. Respir. Crit. Care Med.(in press). (1998)

[Publications] H. Maeda, and T. Akaike: "Nitric oxide and oxygen radicals in infection, inflammation and cancer" Biochemistry (Moscow). (in press). (1998)

[Publications] H. Maeda and T. Akaike: "Nitric Oxiden in Transplant Rejection and Anti-tumor Defense (eds. J.L. Zweier and S.J. Lukiewicz)" Kluwer Academic Publishers, Norwell (in press), (1998)

[Publications] T. Akaike and H. Maeda: "Nitric Oxide and Infection (ed. F.C. Fang)" Plenum Publishing Co., New York (in press), (1998)

赤池孝章熊本大学, 医学部, 助教授 (20231798)