REGULATION OF EGLN-3 IN CARDIAC MUSCLE AND 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。

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.