Effect of G6PD-Deficiency on Cellular Redox Homeostasis and Fuction

During the last 3 year (2007-present), my laboratory has established several G6PD knock-down cell lines (please see PI’s recent publication, # 4, 5, 8, 10, 11). Moreover, we have used these cell lines as model and have clearly documented that G6PD status not only affects red cells but also affects nucleated cells. We have found that G6PD knock-down or G6PD deficient cells are more susceptible to viral infection and show enhanced susceptibility to oxidative damage due to ineffective GSH regeneration (please see PI’s recent publication, # 4-7 ). In addition to the cyto-toxic effects of enhanced oxidative stress due to decreased G6PD activity, we have also found that decreased G6PD activity could affect the cyto-regulatory aspect of oxidative stress (please see Preliminary Results"). The primary goal for the current proposed grant application is to further delineate the role of G6PD in cellular physiology, with a major emphasis on the cyto-regulatory aspect. 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. Toward this end, we want to investigate how changes in cellular G6PD activity may affect protein expression and metabolism. More specifically, we will use proteomic technique to investigate how change in G6PD activity can modulate protein expression including oxidative post translational modifications of proteins such as phosphorylation/dephosphorylation, and glutathionylation. At the same time, we will use metabolomic technique to delineate how changes in G6PD activity can alter certain metabolic pathways which are regulated by redox signaling. By completing this project, we can gain insight into the relationship between G6PD status, redox homeostasis and many cellular functions. Moreover, we will be able to follow-up with interventive measures to ameliorate the impairment of altered redox control in G6PD deficient cells.

Project ID:PC10101-2087
External Project ID:NSC100-2320-B182-010-MY3