REGULATION OF EGLN-3 IN CARDIAC MUSCLE AND ISCHEMIA

EGLN-3 在心肌和缺血中的调节

• 批准号: 7054882
• 负责人: MOHAN C RAO
• 金额: $ 5.2万
• 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/7054882
• 关键词: angiotensin II; cardiac myocytes; cardiovascular pharmacology; disease /disorder model; gene expression; genetic regulation; genetically modified animals; glucose transporter; hypoxia inducible factor 1; isoproterenol; laboratory mouse; myocardial ischemia /hypoxia; myocardium; oxygenases; postdoctoral investigator; procollagen; tissue /cell culture; vascular endothelial growth factors; vascular smooth muscle

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）：本提案的目的是检查 EGLN-3 在心肌中的调节和生物学作用。 EGLN-3 是 Egl-9 (EGLN) 基因家族的成员，该基因家族编码具有脯氨酰羟化酶活性的细胞内蛋白。这导致 HIF-1 α 通过泛素蛋白酶体途径降解，并减弱 HIF-1 α 反应基因，如血管内皮生长因子 (VEGF) 和促红细胞生成素。 EGLN-3 在缺氧中调节的确切作用尚不清楚，缺氧中 EGLN-3 的上调是否具有保护性或保护性仍有待确定。 有害的。我们推测EGLN -3 在心肌中受到调节并在心肌对缺血的反应中发挥作用。为了研究这一点，我们提出以下目标：1）检查EGLN-3在心肌中的调节。2）检查EGLN-3在心肌缺血模型中的调节以及3）检验EGLN-3调节心肌对缺血的反应的假设。