Figure 5. Selective decrease of glutathione levels is required for chelerythrine chloride-induced death of TSC2-null cells.
A) Metabolomic analysis was performed on Tsc2-null and Tsc2+/+ MEFs treated with vehicle or chelerythrine chloride (1 uM, 4 h, n=3 per condition). Metabolite levels were normalized to vehicle-treated cells. Glutathione and reduced glutathione levels were significantly lower in Tsc2-null MEFs treated with chelerythrine chloride vs. Tsc2+/+ treated MEFs treated with chelerythrine chloride. B) Tsc2-null MEFs and 621-101 cells were treated for 20 hours with DMSO, chelerythrine chloride (2 uM for MEFs or 5 uM for 621-101), glutathione (GSH, 1 mM), or chelerythrine chloride plus GSH. GSH protects both types of TSC2-null cells from chelerythrine chloride-induced death.