Regulation of Antioxidant Defense in Red Blood Cells by Oxygen and Nitric Oxide

Principal Investigator(s):

Stephen Rogers, Ph.D. - Pediatrics

Status: Completed

Center(s): Center for Pediatric Pulmonary Disease

Award Mechanism: Postdoctoral Fellowship

Project Period: 2/1/2009 - 1/31/2011

Total Amount: $60,000

Collaborators: Allan Doctor

Project Summary:
During circulation, red blood cells (RBCs) journey across diverse and occasionally harsh chemical environments. RBCs have several systems to defend themselves from potentially damaging chemical attack. One of the most important defense systems (the glutathione system) is fundamentally linked to glucose metabolism within RBCs. Glucose metabolism switches between two pathways with oxygen uptake from the lungs and its delivery to the body. While fully oxygenated, RBCs can efficiently maintain cellular defenses during chemical attack. However, we have recently shown that if full oxygenation does not occur in the lungs, RBCs lose resistance to chemical attack. This interferes with several newly appreciated functions of RBCs, including the regulation of blood flow and thus oxygen delivery. Additional preliminary data suggests that the signaling molecule, nitric oxide (NO), supports defense systems in partially oxygenated RBCs. Drs Rogers and Doctor will study this important regulatory mechanism by investigating i) the ability of different physiologically relevant NO species to allow partially oxygenated RBCs to defend themselves from chemical attack, and ii) to identify the specific mechanism by which NO supports defense systems in partially oxygenated RBCs. This project has broad implications for an array of diseases which affect children, including all conditions resulting in respiratory failure, hemoglobinopathies, disorders in glucose metabolism, and also for transfusion medicine. Additionally this work also offers potential novel therapeutic strategies centered upon the manipulation of RBC glucose metabolism.