FIGURE 6:

Inhibition of the pentose phosphate pathway phenocopies inhibition of FA oxidation. (A) Schematic representation of PPP, with targets of DHEA and NAC indicated. NADPH is used in production of reduced glutathione, reductive fatty acid synthesis, and production of 11-β-hydroxysteroids from 11-ketoglucocorticoids. (B) Cells were treated with 150 μM DHEA for 4 h, and then 2 mM DTT was added for 1 h. Reduced and oxidized forms of albumin were detected by immunoblot following modification of lysates with PEG-maleimide as in Figure 4B. (C) Cells were treated in triplicate with 150 μM DHEA in the presence or absence of TM. Xbp1 splicing was detected by RT-PCR. (D) Cells were treated with TM in the presence of increasing concentrations of DHEA (50, 150, 500 μM), and the expression of Bip, Chop, and Wars mRNA was quantitated by qRT-PCR.