Cells cultured without selenium supplementation do not fully incorporate Sec in TrxR but instead incorporate Cys, so lowering the cellular concentration of the selenolthiol form of TrxR. 62 RX1 signal was four times higher in cells supplemented with selenium than without (Fig. ), whereas SS00 and G1 were essentially unaffected. This is consistent with an interpretation that RX1 activation in cells depends on native TrxR, while the mechanistic control G1 (just like nonselective SS00) is not selective in the cellular context for TrxR (presumably, the residual GSH lability of G1 allows it to be activated by the monothiol background; Fig. ).