Tissue Protection and Cell Death Pathways in Myocardial Ischemia

Summary: The excess generation of Reactive oxygen species (ROS) can damage cell components and disrupt cellular functions. Methionine in proteins is easily oxidized by ROS and converted to methionine sulfoxide. The enzyme peptide Methionine Sulfoxide Reductase reduces methionine sulfoxide back to methionine. We report here that MsrA over expression in rat cardiac myocytes prevents damage from ROS and increases cell viability after hypoxic/reoxygenation events. The nonsteroidal anti-inflamatory drug (NSAID) sulindac contains a methyl sulfoxide moiety that can scavenge ROS. Sulindac can be reduced by MsrA and contribute as an antioxidant in the cell. Our results demonstrate that 1 OOuM sulindac can reduce cell death in rat cardiac myocytes during hypoxia/reoxygenation, and ischemia/reperfusion in Langendorf[ perfusions. The BNIP proteins are pro-apoptotic members of the Bcl-2 family of apoptosis regulating proteins. Hypoxia/acidosis stabilizes BNIP-3 and increases its association with the mitochondria, causing the release of cytochrome C and cell death. We report the retrograde perfusion Langendorffmodel is inconclusive in mouse hearts.
2006
Charles E. Schmidt College of Science
Degree granted: Thesis (M.S.)--Florida Atlantic University, 2006.