Analysis of RBC Derived Microparticles from Sickle Cell Mice using Mass Spectrometry: The Impact of Sickle Cell Disease Induced Oxidative Stress on MP Proteome

Proteomics Interest Group Polymerization of sickle cell hemoglobin S (HbS) is recognized as a key event in the pathophysiology of sickle cell disease (SCD). Repeated HbS polymerization promotes an altered red blood cell (RBC) membrane, hemolysis, and microparticles (MP) formation, which have been shown to play a significant role in the interaction of RBCs with vascular endothelium and progression of vaso-occlusive events. We have recently reported that free HbS oxidizes faster, remains locked in a highly oxidizing form (ferryl) longer and loses heme faster than normal HbA. The first part of this seminar will focus on the Laboratory of Biochemistry and Vascular Biology ’ s (LBVB) objectives, strategy and workflow for characterizing the RBC derived microparticle proteomes of SCD and control blood. This seminar, will also focus on proteomic differences between Microparticles derived from wildtype and SCD transgenic mouse models. Finally, we extended this study to characterize the impact of hydroxyurea treatment. The goal of these LBVB studies is to determine the global impact of HbS oxidation on the proteome (relative to wildtype control blood) and to access how hydroxyurea treatment changes the overall proteome associated with SCD. The results from this seminar will ultimately provide new mechanistic insight into molecular details (at the proteome level) of SCD and potential hydroxyurea treatment.Air date: 4/5/2018 9:30:00 AM
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