| Project/Area Number |
12470038
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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 |
Pathological medical chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
AKAIKE Takaaki School of Medicine, Associate Professor, 医学部, 助教授 (20231798)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Hiroshi School of Medicine, Professor, 医学部, 教授 (90004613)
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 |
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥6,500,000 (Direct Cost: ¥6,500,000)
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| Keywords | OXIDATIVE STRESS / GENETIC MUTATION / MUTAGENESIS / VIRAL MUTATION / MOLECULAR EVOLUTION / NO / 8-MTROGUANOSINE / NITRATIVE STRESS / 8-nitroguanine / 抗8-nitroguanine抗体 / 酸素ラジカル / 分化進化 / 塩基損傷 |
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| 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.
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