Effects of G6PD Deficiency on Redox Homeostasis and Function of Cells as Well as Organism

  • Chiu, Daniel Tsun-Yee (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

During the last granting period from 2007-2010, my laboratory developed RNAi and Telomerase techniques to established several immortal G6PD cell lines which allowed us to first discover that G6PD-deficient cells are more susceptible to viral infection. During the current granting period (2010-now), my laboratory has continued our effort in searching for more evidence to support our 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. In the last couple of years, our laboratory has applied nomic technologies to document that G6PD can affect protein expression and certain subsequent metabolism such as alpha toxin detoxification. We have also found that upon encountering exogenous oxidant, G6PD cells exhibit major alterations in global metabolome. Our biggest breakthrough during this granting period is the establishment of a G6PD-deficient C. elegans animal model so that we can extend our studies from cells to animal. More importantly, we have discovered that G6PD deficiency can severely affect embryonic development in C. elegans. The current grant application details our research plan (2014-2017) and emphasis that we will continue to delineate the biochemical and physiological roles of G6PD in cells and animal model. The four Specific Aims for the current proposal are list below: 1. To investigate how does G6PD affect NOX in different cells upon oxidant challenge and the subsequent signal transduction via the NOX pathway. (All will be completed in the 1st year) 1a. To prove the increased susceptibility of G6PD deficient cells to viral infection is due to the effects of G6PD on redox homeostasis rendering cellular innate immunity abnormal. 1b.To investigate whether the delayed TNF- induced inflammatory responds is due to the effect of G6PD on NOX. 1c. Using lipid-over loaded liver cells as an inflammation model to examine how does G6PD knockdown affect cellular inflammatory responses. 2. To delineate how does G6PD knockdown affect protein expression upon exogenous oxidant challenge using proteomic approach. 3. To dissect how does G6PD deficiency affect RBC metabolism upon exogenous oxidant challenge using metabonomic approach. 4. To unravel the underlying mechanism of impaired embryonic development due to G6PD deficiency and to test whether impaired lipid synthesis plays a role in this regard. Upon completion of this proposed project, we will have a much better understanding of the underlying mechanism for G6PD to regulate cellular redox homeostasis and the deleterious effects due to G6PD deficiency, particularly the chronic effects.

Project IDs

Project ID:PC10308-0925
External Project ID:MOST103-2320-B182-026-MY2
StatusFinished
Effective start/end date01/08/1431/07/15

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