System xc- is Regulated by Multiple Mechanisms in U-138 MG Cells
Dr. Leah Chase, Hope College
System xc- is a transporter located on the plasma membrane of many cell types including glioma cells, neurons, fibroblasts, activated macrophages, microglia, and vascular endothelial cells. This transporter is thought to be involved in alleviating oxidative stress in those cell types. An important question that had remained unanswered has been the time course of System xc- activation and subsequent localization to the membrane of the cell following exposure to hydrogen peroxide. Through experiments such as biotinylations and cystine uptake assays, a time course of approximately two hours has been proposed, in which System xc- is trafficked to the membrane and remains there for nearly two hours following hydrogen peroxide exposure. In the process of completing these experiments, a new mechanism of regulation of System xc- was discovered. We demonstrated washing the cells with new media causes a nearly ten-fold increase in transporter activity, without a change in membrane localization. We hypothesize that the activity of the transporter may be influenced by the glutathione concentration of the cell. Further study is ongoing to understand this novel mechanism of regulation of System xc-.
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