FIGURE 6.

eGFP-expressing Txnrd1^−/− cells cannot be rescued from BSO-induced cell death by co-culture with xCT-expressing Txnrd2^−/− cells. A, schematic outline of the co-culture experiment. Under BSO-induced GSH deficiency, xCT-overexpressing cells can rescue control cells from cell death by generating a Cys-rich extracellular environment. B, in co-culture experiments, xCT-overexpressing Txnrd2^−/− were able to rescue eGFP-expressing Txnrd2^−/− (top panel) and Txnrd1^+/− cells (middle panel) from BSO-induced cell death, but not eGFP-expressing Txnrd1^−/− cells (bottom panel). Thus, even in medium conditioned by xCT-Txnrd2^−/− cells and highly enriched for reducing equivalents in the form of Cys, eGFP-Txnrd1^−/− cells cannot survive and proliferate when GSH synthesis is inhibited by BSO treatment.