| Project/Area Number |
12470065
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Kumamoto University |
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Principal Investigator |
MAEDA Hiroshi School of Medicine, Professor, 医学部, 教授 (90004613)
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| Co-Investigator(Kenkyū-buntansha) |
AKAIKE Takaaki School of Medicine, Associate Professor, 医学部, 助教授 (20231798)
宮本 洋一 熊本大学, 医学部, 助手 (20295132)
澤 智裕 熊本大学, 医学部, 助手 (30284756)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | NO / PEROXYNITRITE / HOST DEFENSE / MURINE SALMONELLOSIS / APOPTOSIS / ANTI-APOPTOTIC EFFECT / CYTOPROTECTIVE EFFECT / INOS-DEFICIENT MICE / Helicobacter pylori / パーオキシナイトライト / 免疫抑制 |
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| 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.
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