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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL083592-03
Application #
7416648
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Meadows, Tawanna
Project Start
2006-05-01
Project End
2010-06-30
Budget Start
2008-05-01
Budget End
2010-06-30
Support Year
3
Fiscal Year
2008
Total Cost
$55,852
Indirect Cost
Name
University of Rochester
Department
Internal Medicine/Medicine
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627