Post-translational Regulation of High Output NO and Endothelial Barrier Dysfuncti

高输出 NO 和内皮屏障功能障碍的翻译后调节

• 批准号: 8059128
• 负责人: Randal A Skidgel
• 金额: $ 34.51万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8059128
• 关键词: Address; Adherens Junction; Binding; Binding Sites; Cell Culture Techniques; Clathrin; Collaborations; Complex; Dimerization; Dissociation; Endocytosis; Endothelial Cells; Functional disorder; G-Protein-Coupled Receptors; GTP-Binding Proteins; Generations; Human; Inflammation; Inflammatory; Kinins; Lung; Mediating; Mitogen-Activated Protein Kinases; Modeling; Modification; Molecular Conformation; Mus; NADPH Oxidase; Nitric Oxide; Nitric Oxide Synthase; Output; Pathway interactions; Peptides; Peptidylprolyl Isomerase; Permeability; Peroxonitrite; Phosphorylation; Phosphotransferases; Pinus (genus); Post-Translational Regulation; Principal Investigator; Production; Protein Dephosphorylation; Proteins; Receptor Activation; Role; Scaffolding Protein; Signal Pathway; Signal Transduction; Source; Stimulus; Tail; Translational Activation; Translations; cadherin 5; cytokine; human NOS2A protein; lung injury; lung vascular injury; nitration; novel; novel therapeutics; programs; receptor; scaffold; seryl-proline

The major source of "high-output" nitric oxide (NO) during inflannmatton is inducible NO synthase (iNOS). Although iNOS is a transcriptionally-regulated generator of high NO, we have discovered a novel mode of post- translational, G protein coupled receptor (GPCR)-mediated activation of iNOS via ERK-dependent phosphorylation in endothelial cells. Post-translational activation of INOS results in a further 3- to 5-fold increase in NO concentration over its already high basal amount. In

在炎症过程中，“高输出”的一氧化氮（NO）的主要来源是诱导型NO合酶（iNOS）。 虽然iNOS是一种转录调节的高NO生成器，但我们发现了一种新的后激活模式， 翻译，G蛋白偶联受体（GPCR）介导的激活iNOS通过ERK依赖性 内皮细胞中的磷酸化。INOS的翻译后激活导致另外3至5倍的 增加NO浓度超过其已经很高的基础量。在