Role of mitochondria in cardiac ischemia

线粒体在心肌缺血中的作用

• 批准号: 8383493
• 负责人: Peifeng Li
• 金额: $ 36.82万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-15 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8383493
• 关键词: Animal Model; Apoptosis; Apoptotic; Cardiac; Cardiac Myocytes; Cell Proliferation; Cells; Cessation of life; Crista ampullaris; Cytochromes; Cytosol; Dominant-Negative Mutation; Dynamin; Energy Supply; Functional RNA; Functional disorder; Genes; Goals; Heart; Heart Diseases; Heart Hypertrophy; Heart failure; Ischemia; Kidney; Lead; Maintenance; Mammalian Cell; Mediating; MicroRNAs; Mitochondria; Molecular; Morphogenesis; Myocardial Infarction; Organelles; Oxidative Stress; Pathogenesis; Pathology; Pathway interactions; Physiology; Play; Prevention; Process; Proteins; Publications; RNA Interference; Regulation; Reperfusion Therapy; Reporting; Role; Serum; Skeletal Muscle; Structure; Testing; Therapeutic; Work; base; heart function; innovation; mortality; neoplastic cell; novel; overexpression; prevent; prohibitin; response

Summary Heart failure is a leading cause of mortality worldwide. Myocardial infarction has been proved to be the most common cause of heart failure. The effective therapeutic strategies need to be developed for the prevention and treatment of myocardial infarction. Apoptosis is a type of death form in myocardial infarction. In order to maintain the heart intact in both structure and function, it is necessary to prevent apoptosis so that the heart does not lose cardiomyocytes. It is well known that cardiomyocytes are enriched in mitochondria. Mitochondria on one hand supply energy for the heart function, they on the other hand participate in the initiation of apoptosis. The most recent studies have revealed that mitochondrial abnormal fission plays a critical role in the regulation of apoptosis. However, the role of mitochondrial fission in the cardiac diseases has been less studied. Furthermore, the molecular regulation of mitochondrial fission in cardiomyocytes remains largely unknown. Our long term goal is to study the role of mitochondria in cardiac pathophysiology. Prohibitin is a cardiac abundant protein. The function of prohibitin in the heart has not yet been clarified. miRNAs are involved in the regulation of cardiac physiology and pathology, but it is unknown whether miRNAs are able to regulate mitochondrial fission machinery. We have made observations clearly showing that prohibitin and miRNA levels are altered in response to oxidative stress and cardiac ischemia. Furthermore, prohibitin can prevent mitochondrial fission and apoptosis in cardiomyocytes. We hypothesize that miRNA and prohibitin constitute an axis in the regulation of mitochondrial fission and apoptosis in the heart. Studies under aim-1 and aim-2 will characterize whether prohibitin can be targeted by the miRNA, and their roles in mitochondrial fission and apoptosis. Studies under aim-3 will explore the molecular mechanism by which prohibitin regulate mitochondrial fission and apoptosis. Studies under aim-4 will test whether prohibitin can influence myocardial infarction induced by ischemia/reperfusion. This proposed project will not only help understand mitochondrial fission and its molecular regulation in the heart, but also can lead to further studies to develop the innovative approaches for the interventional treatment of apoptosis-related cardiac diseases such as myocardial infarction.

摘要 心力衰竭是世界范围内死亡的主要原因。心肌梗死有 已被证明是心力衰竭最常见的原因。有效的治疗方法 需要制定预防和治疗心肌梗死的战略。 细胞凋亡是心肌梗死的一种死亡形式。为了保住心脏 无论是结构还是功能都完好无损，必须防止细胞凋亡，使心脏 不会失去心肌细胞。众所周知，心肌细胞富含 线粒体。线粒体一方面为心脏功能提供能量，另一方面它们 另一方面参与细胞凋亡的启动。最新的研究表明 揭示了线粒体异常分裂在细胞周期调控中的重要作用。 细胞凋亡。然而，线粒体分裂在心脏疾病中的作用一直是 研究较少。此外，线粒体分裂的分子调控也是目前研究的热点。 心肌细胞在很大程度上仍不清楚。我们的长期目标是研究 线粒体与心脏病理生理学。Prohibitin是一种心脏富含的蛋白质。这个 禁忌素在心脏中的作用尚不清楚。MiRNAs参与了 心脏生理和病理的调节，但尚不清楚miRNAs是否 能够调节线粒体分裂机制。我们已经清楚地观察到了 表明抑制素和miRNA水平在氧化应激和 心脏缺血。此外，禁止素可以防止线粒体分裂和 心肌细胞的凋亡。我们假设miRNA和Prohibitin构成了一个 AXIS在心脏线粒体分裂和细胞凋亡的调节中的作用。研究项目： AIM-1和AIM-2将表征禁止素是否可以被miRNA靶向，以及 它们在线粒体分裂和凋亡中的作用。根据AIM-3进行的研究将探索 禁止素调控线粒体分裂和细胞凋亡的分子机制。 根据AIM-4进行的研究将测试禁止素是否会影响心肌梗死 缺血/再灌流所致。这个提议的项目不仅将有助于理解 线粒体的分裂及其在心脏中的分子调控，也可以导致进一步 研究开发介入治疗的创新方法 与细胞凋亡相关的心脏疾病，如心肌梗死。