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S-nitrosothiol-regulated pathways in acute lung injury

急性肺损伤中 S-亚硝基硫醇调节途径

基本信息

批准号：
8197703
负责人：
Matthew Wolf Foster
金额：
$ 19.43万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-12-01 至 2013-05-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8197703
关键词：
Acute Acute Lung Injury Adult Respiratory Distress Syndrome Affect Alveolar Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Attenuated Biological Markers Breathing Bronchoalveolar Lavage Fluid Data Development Diffuse Epithelial Cells Gases Gene Proteins Immune response In Vitro Incidence Inflammation Inflammatory Injury Lipopolysaccharides Liquid substance Lung Mass Spectrum Analysis Measures Mediator of activation protein Molecular Target Mus Natural Immunity Nitric Oxide Pathway interactions Patients Peptides Physiological Pneumonia Post-Translational Protein Processing Prevention therapy Property Protein Analysis Protein S Proteins Proteome Proteomics Regulation Resolution Respiratory Failure Risk Role S-Nitrosothiols Saline Sepsis Signal Pathway Signal Transduction Structure of parenchyma of lung Structure of respiratory epithelium Supportive care TLR4 gene Therapeutic Translating Trauma United States abstracting airway epithelium airway inflammation base chemokine design effective therapy ethyl nitrite lung injury mortality mouse model prevent protein expression research study respiratory response transcription factor

项目摘要

Title: S-nitrosothiol-regulated pathways in acute lung injury Abstract (245 words) Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by an initial airway inflammatory insult that results in diffuse alveolar damage and the subsequent development of respiratory failure. Despite an incidence of ~200,000 cases/year in the United States and mortality rate approaching 40%, no effective therapy exists to treat ALI/ARDS. S-nitrosothiols (SNOs) are endogenously-produced, bioactive forms of nitric oxide that function to inhibit immune response pathways in the respiratory epithelium. Recently, we demonstrated that airway SNOs are acutely depleted in a mouse model of ALI and that treatment with inhaled ethyl nitrite (ENO), an S-nitrosylating agent, protects from the development of lung injury. However, the molecular targets of SNOs in the lung airway remain to be discerned. We hypothesize that proteomic signatures derived from analysis of airway lining fluid can be used to elucidate the SNO-regulated immune response pathways in ALI which underlie the pharmacological basis of ENO therapy. Accordingly, we propose to: 1. Characterize the effects of ENO treatment on the airway proteome in ALI and identify signaling pathways that are affected by SNO repletion; and 2. Identify BALF proteins that are modified by S- nitrosylation in ALI and determine the effects of S-nitrosylation on their inflammatory activities.. Completion of these specific aims should provide a fuller understanding of SNO-regulated pathways in the airways and will guide the further study of SNO-based therapy for the prevention and resolution of inflammatory lung injury.

标题：急性肺损伤中的S-亚硝基硫醇调节通路摘要（245字）急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）的特征在于初始气道炎症性损伤导致弥漫性肺泡损伤和随后的呼吸道疾病失败尽管在美国发病率约为20万例/年，死亡率接近40%，目前还没有有效的治疗ALI/ARDS的方法。S-亚硝基硫醇（SNOs）是内源性产生的生物活性物质，一氧化氮的形式，其功能是抑制呼吸道上皮中的免疫反应途径。最近，我们证明了在ALI小鼠模型中气道SNO急性耗竭，吸入的亚硝酸乙酯（ENO）是一种S-亚硝基化剂，可防止肺损伤的发展。但 SNO在肺气道中的分子靶点仍有待识别。我们假设蛋白质组学来自气道衬里液分析的特征可用于阐明SNO调节的免疫应答， ENO治疗的药理学基础。因此，我们建议至：1.表征ENO治疗对ALI中气道蛋白质组的影响并识别信号传导受SNO补充影响的途径;和2.鉴定S-修饰的BALF蛋白亚硝酰化的ALI，并确定S-亚硝酰化对他们的炎症活动的影响。这些具体目标的完成应该提供一个更全面的了解SNO调节途径，并将指导进一步研究基于SNO的治疗，以预防和解决炎性肺损伤

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Solid-phase capture for the detection and relative quantification of S-nitrosoproteins by mass spectrometry.

DOI：
10.1016/j.ymeth.2012.10.001
发表时间：
2013-08-01
期刊：
METHODS
影响因子：
4.8
作者：
Thompson, J. Will;Forrester, Michael T.;Moseley, M. Arthur;Foster, Matthew W.
通讯作者：
Foster, Matthew W.

Methodologies for the characterization, identification and quantification of S-nitrosylated proteins.