Molecular Mechanisms of Redox-Regulation in Viral Pathogenesis
Molecular Mechanisms of Redox-Regulation in Viral Pathogenesis
批准号:
09470046
负责人:
AKAIKE Takaaki
金额:
$3.71万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
1997
资助国家:
日本
项目状态:
已结题
起止时间:
1997 至 1999
中文摘要
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(O-D3-(/)2-D3)and hydroxyl radical(·OH)have been implicated as possible pathogenic molecules in viral disease pathogenesis.Much attention has been given to another simple inorganic radical,i.e.,NO in the 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-γand 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.Our present results indicate that overproduction of NO and oxygen radicals should be a common phenomenon in various infections。反应nitrogen oxide species such as peroxynitrite are prod…More uced in biological systems through the reaction of NO with O I D3-(/)2个D 3.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.In fact,it is revealed in our current study that peroxynitrite is critically involved in the viral pathogenesis through its nonselective injury to the host‘cells and tissues.Thus,understanding of the role of NO and oxygen radical generation in virus infections will provide insight into not only viral pathogenesis but also the host-pathogen interaction in microbial infections at a molecular level.Moreover,among various NO-induced pathological effects,the mutagenic potential of NO in microbial pathogens is also intriguing.For viral mutation,it is of potential interest to investigate a possible association of oxidative stress and virulence of viruses.In this context,our recent study verifies for the first time that oxidative stress induced by high-output NO accelerates RNA virus mutations.Briefly,by using a recombinant RNA virus,Sendai virus(a negative-sense and single-strand RNA virus),containing a marker gene for genetic mutation and iNOS knockout mice,we obtained solid and direct evidence showing that overproduction of NO in the hosts(wild-type mice)in vivo apparently increases and accelerates viral mutation rates compared with the situation in iNOS-deficient mice.This process of accelerated mutation expands the heterogeneity of variants of the pathogen,leading to rapid evolution under selective pressure。NO and O I D3-(/)2个D3-and hence peroxynitrite generation occurs universally in infected hosts.This finding therefore has great implications for the RNA virus evolution in general,including the rapid generation of drug-resistant and immunologically tolerant and cell tropism-altered mutants of HIV in vivo.Less:Less
英文摘要
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 (OィイD3-(/)2ィエD3) and hydroxyl radical (・OH) have been implicated as possible pathogenic molecules in viral disease pathogenesis. Much attention has been given to another simple inorganic radical, i.e., NO in the 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-γ 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. Our present results indicate that overproduction of NO and oxygen radicals should be a common phenomenon in various infections. Reactive nitrogen oxide species such as peroxynitrite are prod … More uced in biological systems through the reaction of NO with OィイD3-(/)2ィエD3. 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. In fact, it is revealed in our current study that peroxynitrite is critically involved in the viral pathogenesis through its nonselective injury to the host'cells and tissues. Thus, understanding of the role of NO and oxygen radical generation in virus infections will provide insight into not only viral pathogenesis but also the host-pathogen interaction in microbial infections at a molecular level. Moreover, among various NO-induced pathological effects, the mutagenic potential of NO in microbial pathogens is also intriguing. For viral mutation, it is of potential interest to investigate a possible association of oxidative stress and virulence of viruses. In this context, our recent study verifies for the first time that oxidative stress induced by high-output NO accelerates RNA virus mutations. Briefly, by using a recombinant RNA virus, Sendai virus (a negative-sense and single-strand RNA virus), containing a marker gene for genetic mutation and iNOS knockout mice, we obtained solid and direct evidence showing that overproduction of NO in the hosts (wild-type mice) in vivo apparently increases and accelerates viral mutation rates compared with the situation in iNOS-deficient mice. This process of accelerated mutation expands the heterogeneity of variants of the pathogen, leading to rapid evolution under selective pressure. NO and OィイD3-(/)2ィエD3- and hence peroxynitrite generation occurs universally in infected hosts. This finding therefore has great implications for the RNA virus evolution in general, including the rapid generation of drug-resistant and immunologically tolerant and cell tropism-altered mutants of HIV in vivo. Less
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H. Maeda and T. Akaike: "Nitric oxide and oxygen radicals in infection, inflammation, and cancer"Biochemistry (Moscow). 63. 854-865 (1998)
H. Maeda 和 T. Akaike:“感染、炎症和癌症中的一氧化氮和氧自由基”生物化学(莫斯科)。
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赤池孝章: "特集/NO(一般化窒素)NOS阻害剤の臨床応用の可能性"循環器科. 44. 459-466 (1998)
Takaaki Akaike:“NO(广义氮)NOS 抑制剂的临床应用的特点/可能性”心脏病学系 44. 459-466 (1998)。
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H. Sugiura, et al.: "Role of peroxynitrite in airway microvascular hyperpermeability during late allergic phase in guinea pigs"Am. J. Respir. Crit. Care Med.. 160. 663-671 (1999)
H. Sugiura 等人:“过氧亚硝酸盐在豚鼠过敏后期气道微血管通透性过高中的作用”Am。
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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)
T. Akaike 等人:“通过高效液相色谱与金属和格里斯试剂的流动反应器联用对各种亚硝基硫醇进行纳摩尔定量和鉴定”J。
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赤池孝章: "IV.炎症に関与する物質(室田誠逸、柏崎禎夫編)"(株)医薬ジャーナル社(東京). 11 (1997)
Takaaki Akaike:“IV. 与炎症有关的物质(由室田精一和柏崎贞雄编辑)”Iyaku Journal Co., Ltd.(东京)11(1997)。
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共 83 条
Study of the mechanism of biosynthesis of polysulfurated proteins coupled with translation
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批准号:16K15208
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项目类别:Grant-in-Aid for Challenging Exploratory Research
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资助金额:$2.25万
-
财政年份:2016
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负责人:AKAIKE Takaaki
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依托单位:
Novel signaling pathway of bacterial stress responses and host defense via autophagy
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批准号:26670207
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项目类别:Grant-in-Aid for Challenging Exploratory Research
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资助金额:$2.33万
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财政年份:2014
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负责人:AKAIKE Takaaki
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依托单位:
Mechanism of intracellular formation of cysteine polysulfide and reactive oxygen species signaling
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批准号:25253020
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项目类别:Grant-in-Aid for Scientific Research (A)
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资助金额:$29.79万
-
财政年份:2013
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负责人:AKAIKE Takaaki
-
依托单位:
Regulation mechanism by hydrogen sulfide anion of electrophilesignaling
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批准号:23651239
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项目类别:Grant-in-Aid for Challenging Exploratory Research
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资助金额:$2.58万
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财政年份:2011
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负责人:AKAIKE Takaaki
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依托单位:
Molecular mechanism of signal transduction by reactive oxygen species
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批准号:21390097
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$11.9万
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财政年份:2009
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负责人:AKAIKE Takaaki
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依托单位:
Molecular regulatory mechanisms of NO analyzed by using nitronyl nitroxide
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批准号:15087207
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项目类别:Grant-in-Aid for Scientific Research on Priority Areas
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资助金额:$18.43万
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财政年份:2003
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负责人:AKAIKE Takaaki
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依托单位:
Research on a novel mechanism for oxidative stress mediated by NO-induced nucleic acid nitration.
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批准号:15390107
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$2.69万
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财政年份:2003
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负责人:AKAIKE Takaaki
-
依托单位:
Development of analysis for all biologically relevant derivatives of NO
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批准号:12557010
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$3.01万
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财政年份:2000
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负责人:AKAIKE Takaaki
-
依托单位:
Research on microbial mutation and evolution involving oxidative stress
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批准号:12470038
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$6.59万
-
财政年份:2000
-
负责人:AKAIKE Takaaki
-
依托单位:
Viral Pathogenesis and Regulation Mechanism of Free Radicals in Host Responses : Role of Nitric Oxide
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批准号:07670347
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$1.47万
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财政年份:1995
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负责人:AKAIKE Takaaki
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依托单位:
Involvement of virus infection in the pathogenesis of pulmonary fibrosis
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批准号:04670472
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项目类别:Grant-in-Aid for General Scientific Research (C)
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资助金额:$1.34万
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财政年份:1992
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负责人:AKAIKE Takaaki
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依托单位:
国内基金
海外基金
排水条件下化肥的流失及其对环境的影响
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批准号:58979388
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项目类别:面上项目
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资助金额:4.0万元
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批准年份:1989
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负责人:张瑜芳
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依托单位: