权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Research on microbial mutation and evolution involving oxidative stress

氧化应激相关微生物突变与进化研究

基本信息

批准号：
12470038
负责人：
AKAIKE Takaaki
金额：
$ 6.59万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

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.

氧自由基和一氧化氮(NO)在一系列不同的微生物感染中产生过量。自由基生物学中的新兴概念现在正在揭示各种疾病的发病机制。自由基致病力在病毒感染中具有重要意义，因为有证据表明，NO和超氧阴离子等氧自由基是各种传染病发病机制中的关键分子。虽然氧自由基和一氧化氮对细菌和原生动物有抗菌作用，但它们对流感病毒肺炎和其他几种嗜神经病毒感染的病毒感染有相反的作用。在各种病毒感染中，诱导型NO合成酶产生大量的NO，通过与氧自由基和活性氧中间体的相互作用产生高活性的氮氧化物物种，如过氧亚硝酸盐。这些不同活性物种的产生赋予了NO不同的生物学功能。活性氮通过鸟苷等多种生物分子的氧化和硝化作用，引起组织氧化损伤和致突变。最近的证据表明，NO诱导的氧化应激加速了病毒突变，这进一步说明了自由基的独特生物学特性。一氧化氮似乎会影响宿主的免疫反应，从而导致免疫病理后果。例如，据报道，在感染期间，NO可以抑制1型辅助T细胞依赖的免疫反应，导致2型辅助T细胞偏向的免疫宿主反应。因此，NO诱导的免疫抑制可能有助于病毒感染的发病机制，并有助于扩大病毒病原体的拟态种群。在本研究中，我们确实成功地阐明了NO在病毒性疾病的发病机制和病毒突变中的关键作用，这与NO的核酸修饰有关，即硝化鸟苷形成8-硝基鸟苷。