REGULATION OF EGLN-3 IN CARDIAC MUSCLE AND ISCHEMIA

EGLN-3 在心肌和缺血中的调节

• 批准号: 7237367
• 负责人: MOHAN C RAO
• 金额: $ 5.4万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7237367
• 关键词: Adult; Angiotensin II; Arterial Fatty Streak; Arteries; Blood Vessels; Brain Hypoxia-Ischemia; Cardiac; Cardiac Myocytes; Cells; Cloning; Contractile Proteins; Data; Erythropoietin; Exhibits; Gene Family; Genes; Glucose Transporter; Hela Cells; Hypoxia; Hypoxia Inducible Factor; Ischemia; Isoproterenol; Laboratories; Modeling; Muscle Development; Myocardium; PC12 Cells; Pathway interactions; Pheochromocytoma; Platelet-Derived Growth Factor; Play; Procollagen-Proline Dioxygenase; Proteins; Rattus; Regulation; Reporting; Role; Skeletal Muscle; Skeletal system; Smooth Muscle Myocytes; Testing; Thinking; Transcriptional Activation; Ubiquitin; Up-Regulation; Vascular Endothelial Growth Factors; attenuation; hypoxia inducible factor 1; injured; member; multicatalytic endopeptidase complex; myogenesis; osteosarcoma; response; transcription factor

DESCRIPTION (provided by applicant): The objective of this proposal is to examine the regulation and biologic role of EGLN-3 in cardiac muscle. EGLN-3 is a member of the Egl-9 (EGLN) gene family that encodes intracellular proteins that exhibit prolyl hydroxylase activity. This results in the degradation of HIF-1 alpha via the ubiquitin proteosome pathway and attenuation of HIF-1 alpha responsive genes, such as vascular endothelial growth factor (VEGF) and erythropoietin.The exact role of EGLN-3 regulation in hypoxia is unclear and it remains to be determined whether the up-regulation of EGLN-3 in hypoxia is protective or deleterious. We hypothesize that EGLN -3 is regulated in cardiac muscle and plays a role in the response of cardiac muscle to ischemia . In order to study this we propose the following aims:1) To examine the regulation of EGLN-3 in cardiac muscle.2) To examine the regulation of EGLN-3 in models of cardiac ischemia and 3) To test the hypothesis that EGLN-3 regulates the response of cardiac muscle to ischemia.

描述（由申请人提供）：本提案的目的是研究EGLN-3在心肌中的调节和生物学作用。EGLN-3是Egl-9 （EGLN）基因家族的一员，该基因家族编码具有脯氨酸羟化酶活性的细胞内蛋白。这导致HIF-1 α通过泛素蛋白体途径降解，HIF-1 α应答基因（如血管内皮生长因子（VEGF）和促红细胞生成素）的衰减。EGLN-3调控在缺氧中的确切作用尚不清楚，EGLN-3在缺氧中的上调是保护作用还是有害作用尚不清楚。我们假设EGLN -3在心肌中受到调控，并在心肌缺血反应中发挥作用。为此，我们提出以下研究目的：1)研究EGLN-3在心肌中的调控作用。2)探讨EGLN-3在心肌缺血模型中的调节作用；3)验证EGLN-3调节心肌缺血反应的假说。