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It has been shown that dehydroepiandrosterone (DHEA) is an inhibitor of G6PD. Th

ID: 474847 • Letter: I

Question

It has been shown that dehydroepiandrosterone (DHEA) is an inhibitor of G6PD. The investigators incubated cells with DHEA, then lysed the cells and measured G6PD and PGD enzymatic activity in terms of the change in absorbance at 341 nm. In a separate experiment, the incorporation of [^3H]-thymidine was measured in the presence of PGDF (platelet derived growth factor, which stimulates cell growth) and increasing concentrations of DHEA. The results are shown in Figures 32.4 and 32.5, respectively. A Western blot analysis was also carried out (data not shown), in winch the investigators found that there was no change in enzyme protein in cells exposed to either PGDF, or DHEA, or both. What is your interpretation of the results shown in these two figures? Again, be quantitative in your assessment of the data. Figure 32.4: Dose-response curves of the effect of DHEA on G6PDH and PGD activity. Cell lysates were analyzed for enzyme activity in the presence of varying amounts of DHEA (from Tian, et al., 1998). Figure 32.5: Scrum-starved cells were treated with DHEA in the presence of PGDF for 12 hours, then [^3 H]-thymidine was added and the cells were incubated for an additi4nal 12 hours (from Tian, et at., 1998).

Explanation / Answer

As we can see from figures DHEA is inhibiting G6PDH. As the concentration of DHEA increases 10 fold (from 1.0E-08 to 1.0E-07) the activity is also decreased from 80/min to @ 70/min.

But real decrease happens at 1.0E-05 concentration.

PGD doesn’t seem following the same pattern as G6PDH though.

[3H]-thymidine which is indicator of cell growth clearly shows action of DHEA. Increasing concentration of DHEA by 10 fold does decrease [3H]-thymidine from 27000/well to 22000/well and it is decreasing steadily as per concentration increases.

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