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A decrease in glucose 6-phosphate dehydrogenase activity and mRNA is an early event in phorbol ester-induced
T A Bremner1, N D'Costa, L A Dickson
1Department of Biology, Howard University, Washington, DC 20059, USA.
Life Sciences
|January 1, 1996
Summary
A decrease in Glucose-6-phosphate dehydrogenase (G6PD) activity accompanies the loss of the transformed phenotype in leukemia cells. This suggests high G6PD levels are linked to neoplastic transformation.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- The glutathione redox system (GRS) regulates gene expression through protein redox modification.
- Elevated Glucose-6-phosphate dehydrogenase (G6PD) levels in preneoplastic lesions are hypothesized to drive neoplastic transformation.
Purpose of the Study:
- To investigate the relationship between G6PD activity and the loss of the transformed phenotype during induced differentiation.
- To test if decreased G6PD activity accompanies the acquisition of a normal phenotype in leukemia cells.
Main Methods:
- Utilized THP-1 human promonocytic leukemia cells as a model for induced macrophage differentiation.
- Measured specific activities of GRS enzymes (G6PD, glutathione peroxidase, glutathione reductase) during phorbol ester-induced differentiation.
- Assessed changes in G6PD mRNA levels.
Main Results:
- Observed an 80% decrease in G6PD activity during early differentiation.
- Noted an increase in apparent KM for glucose 6-phosphate, indicating altered G6PD kinetics.
- Found a fourfold reduction in steady-state G6PD mRNA levels preceding phenotype normalization.
Conclusions:
- Findings support the hypothesis linking high G6PD levels to neoplastic transformations.
- Reduced G6PD activity is associated with the loss of the transformed phenotype in THP-1 cells.
- G6PD regulation at the mRNA level plays a role in this process.