Figure 5.

Glutamine and α-ketoglutarate inhibit cystine-induced NADPH depletion. A, cells were placed in glucose- and amino acid-free medium with or without glutamine (2 mm), cystine (0.2 mm), or dm-αKG (4 mm) for 24 h. Quantification of cell death was performed using an LDH release assay. B–D, after the medium was replaced with glucose- and amino acid-free medium containing glutamine (2 mm), cystine (0.2 mm), dm-αKG (4 mm), or EGCG (20 μm) for 2 (B) or 1 h (C and D), the NADP⁺/NADPH ratio was measured. Error bars represent S.D. (n = 3). *, p < 0.05; **, p < 0.01; ***, p < 0.001, calculated by one-way ANOVA with Tukey's post hoc test. E, model of xCT-mediated cell death under glucose deprivation conditions. Glc, glucose; AA, amino acids.