Reactive oxygen species drive muscle metabolism

活性氧驱动肌肉新陈代谢

• 批准号: 10359197
• 负责人: SIOBHAN M CRAIGE
• 金额: $ 12.37万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-25 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10359197
• 关键词: Address; Applications Grants; Attenuated; Blood Vessels; Breeding; Cardiovascular Diseases; Data; Development; Diabetes Mellitus; Disease; Electric Stimulation; Enzymes; Exercise; Gene Expression; Genes; Genetic Transcription; Glucose; Goals; Hand; Health; Hydrogen Peroxide; Immunology; Inflammasome; Inflammation; Inflammatory; Investigation; Knockout Mice; Knowledge; Lead; Link; Mediating; Mentors; Metabolic; Metabolic Pathway; Metabolic dysfunction; Metabolism; Molecular Biology; Mus; Muscle; Muscular Atrophy; Musculoskeletal Diseases; NADPH Oxidase; Natural regeneration; Obesity; Oxidation-Reduction; Physical activity; Production; Reactive Oxygen Species; Records; Reporter; Research; Role; Signal Transduction; Signaling Molecule; Skeletal Muscle; Techniques; Testing; Therapeutic; Time; Tissues; Training; Work; age-related muscle loss; angiogenesis; career; cell type; combat; cytokine; design; exercise capacity; frailty; glucose tolerance; improved; insight; live cell imaging; muscle aging; muscle metabolism; muscle physiology; novel; novel strategies; novel therapeutics; obesity prevention; prevent; programs; response; skeletal muscle metabolism; success; tool; transcriptome sequencing

PROJECT SUMMARY Exercise is one of the most powerful tools to prevent muscle loss and aging-related diseases. Reactive oxygen species (ROS) and inflammation, long-thought to contribute to tissue damage, have recently been recognized to function as signaling molecules necessary for the benefits of exercise. My preliminary data demonstrate that improved glucose tolerance and exercise capacity, two hallmarks of exercise-induced muscle adaptation, are attenuated in mice deficient in NADPH oxidase 4 (Nox4), an ROS-producing enzyme. My data indicate that Nox4 drives an Nlrp3 muscle cytokine response that leads to improved muscle metabolism. In this proposal, I will investigate the role of redox-mediated adaptation to exercise using state-of-the art techniques in immunology and muscle physiology (e.g., Amnis/Immagestream, RNA-seq, and ex vivo muscle stimulation). To aid me in completion of this project, I have established a strong mentoring team comprised of experts in the fields of inflammation and immunology (Dr. Katherine Fitzgerald), muscle molecular biology and regeneration (Dr. Charles Emerson), skeletal muscle adaptation to exercise and redox signaling (Dr. Zhen Yan) and immunometabolism (Dr. Michael Czech), all of whom are top leaders in their respective fields and have lengthy track records of mentoring success. My career goal is to lead a successful research program dedicated to the investigation of redox and inflammatory signaling in angiogenesis and skeletal muscle adaptation. I believe that the knowledge gained by understanding the details of ROS signaling in adaptation to exercise will lead to the development of better therapeutic strategies to combat frailty, diabetes, obesity, and musculoskeletal diseases.

项目摘要 运动是防止肌肉损失和与衰老有关的疾病的最强大工具之一。活性氧 最近已经认识到物种（ROS）和炎症，长期以来对组织损害造成了贡献 充当运动益处所需的信号分子。我的初步数据表明 葡萄糖耐量和运动能力的提高，运动引起的肌肉适应的两个标志是 在缺乏NADPH氧化酶4（NOX4）的小鼠中减弱，一种产生ROS的酶。我的数据表明 NOX4驱动NLRP3肌肉细胞因子反应，从而改善肌肉代谢。在这个建议中，我 将研究氧化还原介导的适应性在使用最先进的技术中进行锻炼的作用 免疫学和肌肉生理学（例如，AMNIS/Immagestream，RNA-Seq和Ex Vivo肌肉刺激）。 为了帮助我完成该项目，我建立了一个由专家组成的强大指导团队 炎症和免疫学领域（凯瑟琳·菲茨杰拉德博士），肌肉分子生物学和再生 （Charles Emerson博士），骨骼肌适应运动和氧化还原信号（Zhen Yan博士）和 免疫代谢（Michael Czech博士），他们都是各自领域的顶级领导者 指导成功的记录。 我的职业目标是领导一项成功的研究计划，致力于调查氧化还原和 血管生成和骨骼肌适应中的炎症信号传导。我相信所获得的知识 了解适应运动中ROS信号的细节将导致更好的发展 打击脆弱，糖尿病，肥胖和肌肉骨骼疾病的治疗策略。