Metabolism Core

新陈代谢核心

• 批准号: 10612117
• 负责人: DANIEL RAFTERY
• 金额: $ 19.26万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-05 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10612117
• 关键词: Address; Amino Acids; Apoptosis; Atrophic; Bile Acids; Biochemical; Biological; Biological Assay; Biology; Biopsy; Cardiolipins; Cell physiology; Cells; Cellular Metabolic Process; Coenzymes; Collaborations; Complement; Consumption; Coupling; Data; Data Collection; Devices; Disease; Equilibrium; Experimental Designs; Fiber; Functional disorder; Genus Hippocampus; Goals; Health; Hemoglobin; Homeostasis; Individual; Institution; Ligaments; Link; Lipids; Magnetic Resonance; Mass Spectrum Analysis; Measurement; Measures; Mechanics; Metabolic; Metabolic Pathway; Metabolism; Methods; Mitochondria; Modeling; Molecular; Monitor; Mus; Muscle; Muscle Fibers; Myoglobin; Myopathy; Optics; Oxidation-Reduction; Oxidative Phosphorylation; Oxidative Stress; Oxygen; Pathology; Pathway Analysis; Permeability; Phosphorylation; Production; Protein Biosynthesis; Reactive Oxygen Species; Research; Research Personnel; Respiration; Rest; Role; Sampling; Skeletal Muscle; Spectrum Analysis; Spirometry; Statistical Data Interpretation; Statistical Methods; Stress; System; Systems Biology; Tendon structure; Therapeutic; Therapeutic Intervention; Training; Universities; Washington; acylcarnitine; aqueous; base; biomarker discovery; improved; in vivo; insight; lipidomics; metabolomics; mitochondrial dysfunction; mouse model; muscle degeneration; muscle metabolism; muscle physiology; prevent; protein degradation; tool

ABSTRACT – Core C The ability to maintain metabolic and redox homeostasis is at the center of muscle health and degeneration. The Metabolism Core will provide access to unique state of the art tools to quantify altered metabolism and mitochondrial function in skeletal muscle. Disruption of energy homeostasis due to mitochondrial dysfunction is a key mechanism controlling diverse cellular processes that can lead to muscle degeneration, including the balance between protein synthesis and degradation, contractile function, E-C coupling, and apoptosis. The Metabolism Core will provide an integrative approach to analyze the role of changes in metabolic and mitochondrial function in skeletal muscle dysfunction to a broad user base. We have developed state of the art tools that include global and targeted metabolomics, magnetic resonance and optical spectroscopy, and biochemical analyses of isolated mitochondria and permeabilized fibers that will provide vastly improved and detailed insights into muscle biology, and an ability to monitor therapeutic approaches at the molecular level. The goal of this core is to expand access to these tools and expertise for experimental design, data collection, analysis, and interpretation to address the role of metabolism in skeletal muscle health and dysfunction. Aim 1 will provide a broad array of targeted and global metabolomic and lipidomic analyses from skeletal muscle biopsy, ligaments and tendons, as well as biofluids and related biological samples. Aim 2 will provide state of the art analyses of in vivo mitochondrial capacty and quality (ATPmax and P/O) and muscle energety state (PCr/ATP and ADP/ATP). Aim 3 will provide detailed biochemical analyses of oxidative phosphorylation and mitochondrial oxidative stress in permeabilized muscle fibers and isolated mitochondria. These measurements will provide an integrated picture of muscle metabolism, mitochondrial function and muscle energetics that can be used to understand the mechanisms leading to protection or pathology in models of skeletal muscle disease. The central role of metabolism connecting all aspects of muscle physiology will allow this Core to provide a natural bridge between between the Mechanics and Devices and Quantitative Analysis Cores of the proposed center.

摘要 – 核心 C 维持代谢和氧化还原稳态的能力是肌肉健康和退化的核心。 新陈代谢核心将提供独特的最先进的工具来量化改变的新陈代谢和 骨骼肌中的线粒体功能。由于线粒体功能障碍导致能量稳态的破坏 控制多种细胞过程的关键机制，可导致肌肉退化，包括 蛋白质合成与降解、收缩功能、E-C 耦合和细胞凋亡之间的平衡。这 代谢核心将提供一种综合方法来分析代谢和代谢变化的作用 线粒体在骨骼肌功能障碍中的功能具有广泛的用户基础。我们开发了最先进的技术 包括全局和靶向代谢组学、磁共振和光谱学的工具，以及 对分离的线粒体和透化纤维进行生化分析，这将大大改善和 对肌肉生物学的详细见解，以及在分子水平上监测治疗方法的能力。 该核心的目标是扩大对这些工具和专业知识的访问，以进行实验设计、数据收集、 分析和解释，以解决代谢在骨骼肌健康和功能障碍中的作用。目标1 将提供广泛的骨骼肌靶向和全局代谢组学和脂质组学分析 活检、韧带和肌腱，以及生物体液和相关生物样本。目标 2 将提供以下状态 体内线粒体容量和质量（ATPmax 和 P/O）以及肌肉能量状态的艺术分析 （PCr/ATP 和 ADP/ATP）。目标 3 将提供氧化磷酸化的详细生化分析和 透化肌纤维和分离线粒体中的线粒体氧化应激。这些测量 将提供肌肉代谢、线粒体功能和肌肉能量的综合图像， 可用于了解骨骼肌疾病模型中导致保护或病理的机制。 连接肌肉生理学各个方面的新陈代谢的核心作用将使该核心能够提供 拟议的力学和设备与定量分析核心之间的天然桥梁 中心。