G6PD-Deficient Cells as Model Systems to Delineate the Effects of Oxidative Stress on Cells

During the last few years, my laboratory has clearly documented that G6PD-defciency not only affects red blood cells but also affects nucleated cells. On the clinical aspect, G6PD-deficiency not only just manifests on the hemolytic anemia aspect, but also manifests other clinical presentations such as poor prognosis in nasopharyngeal carcinoma and increased risk for diabetes. In order to investigate how change in G6PD activity may affect cellular redox status which in turn may play a key regulatory role in many cellular functions, my laboratory has established G6PD-deficient primary culture and G6PD-knockdown cell lines. The primary goal of this project is to further delineate the role of G6PD in cellular physiology. We want to test our working hypothesis that G6PD is a major player in regulating cellular redox homeostasis by maintaining proper NADPH to NADP+ ratio which in turn plays a key role in the regulation of many cellular events. More specifically, we want to investigate how changes in cellular G6PD activity may affect gene transcription, protein expression and eventually metabolism. In this regard, we will focus our attention on NADPH dependent systems, GSH synthetic pathway and redox sensitive genes/proteins. In addition, antioxidants from natural products will be screened for the one which offers the best cellular protection to G6PD-deficient cells and G6PD-knockdown cells. Still more, we want to use G6PD-knockdown cells as model to identify markers of oxidative stress/damage. By doing so, we can gain insight into the relationship between G6PD status, redox balance and many cellular functions. Moreover, we will be able to suggest protective measures to prevent oxidative damage for cells, or even individuals, which (who) are particularly susceptible of oxidative injury. Last but not the least, we may be able to identify markers of oxidative stress/damage which should be very helpful in the early diagnosis of degenerative diseases such as cancer and cardiovascular disorders.

Project ID:PC9706-0314
External Project ID:NSC96-2320-B182-015-MY3