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)基因家族中的一员，编码细胞内具有Pro羟基酶活性的蛋白。这导致了HIF-1α通过泛素蛋白小体途径的降解和HIF-1α反应基因的减弱，如血管内皮生长因子(VEGF)和红细胞生成素。EGLN-3在缺氧中的确切调控作用尚不清楚，缺氧时EGLN-3的上调是保护还是有害仍有待确定。我们假设EGLN-3在心肌中受到调控，并在心肌对缺血的反应中发挥作用。为了研究这一点，我们提出了以下目的：1)研究EGLN-3在心肌缺血模型中的调节作用；2)研究EGLN-3在心肌缺血模型中的调节作用；3)验证EGLN-3调节心肌对缺血的反应的假说。

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.