xiang-gu@uiowa.edu
Mentor: Steven Lentz, M.D./Ph.D.
Lab Room: 3160 ML
Lab Phone: 319-335-8857

Role of methionine oxidation in atherothrombosis

Inflammatory and oxidative pathways within the atherosclerotic vascular wall generate reactive oxygen species, including superoxide, hydrogen peroxide, peroxynitrite, and hypochlorous acid. These ROS can target methionine residues in vascular proteins, producing protein-bound methionine sulfoxide, often leading to structural changes that adversely affect protein function. Because methionine sulfoxide can be restored to methionine by the action of methionine sulfoxide reductases (MSR), we hypothesize that modification of endothelial proteins, such as thrombomodulin or proteins in the NFκB signaling pathway, by methionine oxidation represents a reversible prothrombotic and proinflammatory mechanism in atherosclerosis. By using gene transfer, transgenic, and mass spectrometric approaches, we hope to define the prothrombotic effects of oxidation of methionine residues in thrombomodulin and the NFκB pathway.