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

炎症期间“高输出”一氧化氮 (NO) 的主要来源是诱导型一氧化氮合酶 (iNOS)。 虽然 iNOS 是高 NO 的转录调节发生器，但我们发现了一种新的后转录调节模式。 通过 ERK 依赖性翻译、G 蛋白偶联受体 (GPCR) 介导的 iNOS 激活 内皮细胞的磷酸化。 INOS 的翻译后激活导致进一步 3 至 5 倍 NO 浓度超过其已经很高的基础量。在