NO-Modified Biomolecules and Pulmonary Signaling
NO 修饰的生物分子和肺部信号传导
基本信息
- 批准号:7883563
- 负责人:
- 金额:$ 34.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-07-11 至 2012-06-30
- 项目状态:已结题
- 来源:
- 关键词:A549AblationAchievementAcidsAcute Lung InjuryAdult Respiratory Distress SyndromeAffectAlveolarAlveolar MacrophagesAnti-Inflammatory AgentsAnti-inflammatoryAsthmaBindingBiologicalBleomycinBlood VesselsBronchodilationCell physiologyCellsChemicalsChemistryChronic lung diseaseCystic FibrosisDataDevelopmentDiseaseDisease modelEnzyme ActivationEpithelialEpithelial CellsEquilibriumFunctional disorderGeneticGrowth and Development functionGuanylate CyclaseHeartHemeImmunityInfectionInflammationInflammatoryInjuryLeadLungLung diseasesMaintenanceMediatingMetabolismModelingModificationMolecularMorphogenesisMusNitratesNitric OxideNitrosationOxidation-ReductionOxidoreductasePathogenesisPathologyPathway interactionsPatientsPersistent Fetal Circulation SyndromePhysiologicalPhysiologyPlayPneumoniaProcessProductionPropertyPulmonary EmphysemaPulmonary PathologyPulmonary Surfactant-Associated Protein DReactionResearch Project GrantsRoleSepsisSeriesSignal PathwaySignal TransductionSignaling MoleculeSystemTailTherapeuticTherapeutic InterventionTransplantationType II Epithelial Receptor CellVasodilationbasebiological systemschemokinechemokine receptorcytokinedesignin vivo Modelindium-bleomycininhaled nitric oxidelung injurymacrophagenitrationnovelnovel therapeutic interventionpublic health relevancepulmonary arterial hypertensionpulmonary functionreceptor expression
项目摘要
DESCRIPTION (provided by applicant): The central role that Nitric Oxide (NO) plays within pulmonary physiology is highlighted by the number of functions in which it plays a role including the maintenance of airway tone, blood vessel tone, inflammation, and even lung growth and development. In addition to these important physiological roles NO has also been implicated in a number of pulmonary diseases including ARDS, Asthma, and cystic fibrosis. As yet the molecular mechanisms by which this simple diatomic molecule can produce such a wide range of signals is unclear, furthermore, it is unclear how disruption of NO metabolism may play a role in pathology. It is the hypothesis of this proposal that the redox capabilities of NO allow it to generate a series of novel NO-modified biomolecules and that these molecules themselves have signaling properties. Furthermore, it is contended that disruption of the redox status of the lung alters the production of these molecules such that pulmonary signaling pathways are affected. Therefore the balance of the production of these molecules is critical to pulmonary physiology and their disruption could play a role in the pathogenesis of disease. This proposal seeks to examine such NO- modified biomolecules which have been demonstrated to possess signaling properties within pulmonary cells, namely S-nitrosylated Surfactant Protein D (SNO-SP-D) and nitrolinoleic acid (LNO2). The signaling properties of these molecules in epithelial and inflammatory cells will be examined. Previously it has been shown that NO metabolism is disrupted in a model of pulmonary disease, namely bleomycin-induced acute lung injury. Therefore the involvement of SNO-SP-D and LNO2 within this disease models will be examined. Utilization of mice in which nitrosothiol metabolism is impaired (GSNOR-/-) within this disease model will allow for more detailed examination of the involvement of NO-modified biomolecules in pulmonary pathophysiology. The proposal will therefore examine the following three specific aims: 1) To determine the effects of S-nitrosylation on SP-D signaling in pulmonary cells; 2) To determine the mechanisms of LNO2 on pulmonary cell signaling; 3) To examine the role of NO-modified biomolecules in pathology. Achievement of these aims will allow for a better understanding of how NO-modification of biomolecules plays a role in pulmonary pathophysiology. Ultimately this will allow for more focused NO-based therapeutics within the lung. PUBLIC HEALTH RELEVANCE. Pulmonary inflammation lies at the heart of many diseases that are currently on the rise such as asthma and emphysema. The chemical nitric oxide is an important part of inflammation and this research project will investigate how it controls cellular function within the lung. A greater understanding of these processes may lead to novel therapeutic approaches for inflammatory lung diseases.
描述(由申请人提供):一氧化氮(NO)在肺生理学中发挥的中心作用通过其发挥作用的功能的数量来突出,包括维持气道张力、血管张力、炎症,甚至肺生长和发育。除了这些重要的生理作用,NO还与许多肺部疾病包括ARDS、哮喘和囊性纤维化有关。到目前为止,这种简单的双原子分子可以产生如此广泛的信号的分子机制尚不清楚,此外,还不清楚NO代谢的破坏如何在病理学中发挥作用。这是该提议的假设,即NO的氧化还原能力允许其产生一系列新颖的NO修饰的生物分子,并且这些分子本身具有信号传导特性。此外,据认为,肺的氧化还原状态的破坏改变了这些分子的产生,使得肺信号传导途径受到影响。因此,这些分子的产生的平衡对于肺生理学是至关重要的,并且它们的破坏可以在疾病的发病机制中发挥作用。该提议试图检查已被证明在肺细胞内具有信号传导性质的这种NO修饰的生物分子,即S-亚硝基化表面活性剂蛋白D(SNO-SP-D)和硝基亚油酸(LNO 2)。将检查这些分子在上皮细胞和炎症细胞中的信号传导特性。以前已经表明,NO代谢在肺部疾病模型中被破坏,即博来霉素诱导的急性肺损伤。因此,将检查SNO-SP-D和LNO 2在该疾病模型中的参与。在这种疾病模型中利用亚硝基硫醇代谢受损(GSNOR-/-)的小鼠将允许更详细地检查NO修饰的生物分子在肺病理生理学中的参与。因此,该提案将检查以下三个具体目标:1)确定S-亚硝基化对肺细胞中SP-D信号传导的影响; 2)确定LNO 2对肺细胞信号传导的机制; 3)检查NO修饰的生物分子在病理学中的作用。这些目标的实现将允许更好地理解NO修饰的生物分子如何在肺病理生理学中发挥作用。最终,这将允许在肺内更集中的基于NO的治疗。公共卫生相关性。肺部炎症是许多疾病的核心,目前正在上升,如哮喘和肺气肿。化学一氧化氮是炎症的重要组成部分,该研究项目将研究它如何控制肺内的细胞功能。对这些过程的更深入了解可能会导致炎症性肺病的新治疗方法。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Andrew J Gow其他文献
70 - A Cell Specific Role of INOS in Acute Lung Injury; Recruitment and Activation of Macrophages
- DOI:
10.1016/j.freeradbiomed.2015.10.109 - 发表时间:
2015-10-01 - 期刊:
- 影响因子:
- 作者:
Thea Golden;Andrew J Gow - 通讯作者:
Andrew J Gow
Andrew J Gow的其他文献
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{{ truncateString('Andrew J Gow', 18)}}的其他基金
Obstructive Sleep Apnea and WTC dust: Does Chronic Intermittent Hypoxia exacerbate WTC dust induced lung injury
阻塞性睡眠呼吸暂停和世贸中心粉尘:慢性间歇性缺氧是否会加剧世贸中心粉尘引起的肺损伤
- 批准号:
10459204 - 财政年份:2021
- 资助金额:
$ 34.76万 - 项目类别:
Obstructive Sleep Apnea and WTC dust: Does Chronic Intermittent Hypoxia exacerbate WTC dust induced lung injury
阻塞性睡眠呼吸暂停和世贸中心粉尘:慢性间歇性缺氧是否会加剧世贸中心粉尘引起的肺损伤
- 批准号:
10314852 - 财政年份:2021
- 资助金额:
$ 34.76万 - 项目类别:
NO-Modified Biomolecules and Pulmonary Signaling
NO 修饰的生物分子和肺部信号传导
- 批准号:
8707538 - 财政年份:2008
- 资助金额:
$ 34.76万 - 项目类别:
NO-Modified Biomolecules and Pulmonary Signaling
NO 修饰的生物分子和肺部信号传导
- 批准号:
7526781 - 财政年份:2008
- 资助金额:
$ 34.76万 - 项目类别:
NO-Modified Biomolecules and Pulmonary Signaling
NO 修饰的生物分子和肺部信号传导
- 批准号:
8289980 - 财政年份:2008
- 资助金额:
$ 34.76万 - 项目类别:
NO-Modified Biomolecules and Pulmonary Signaling
NO 修饰的生物分子和肺部信号传导
- 批准号:
8581605 - 财政年份:2008
- 资助金额:
$ 34.76万 - 项目类别:
NO-Modified Biomolecules and Pulmonary Signaling
NO 修饰的生物分子和肺部信号传导
- 批准号:
8098350 - 财政年份:2008
- 资助金额:
$ 34.76万 - 项目类别:
NO-Modified Biomolecules and Pulmonary Signaling
NO 修饰的生物分子和肺部信号传导
- 批准号:
7657295 - 财政年份:2008
- 资助金额:
$ 34.76万 - 项目类别:
Surfactant Proteins and NO in Inflammatory Disease
炎症性疾病中的表面活性蛋白和 NO
- 批准号:
7116878 - 财政年份:2003
- 资助金额:
$ 34.76万 - 项目类别:
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