Effects of glutathione-related compounds on increased caspase-3 and caspase-6-like activities in ricin-treated U937 cells

Both caspase-3 and -6-like activities increased in the cytosolic extract fr om ricin-treated U937 cells that were inhibited by glutathione disulfide (G SSG) in a dose-dependent manner, but reduced glutathione (GSH) had no effec t. Interestingly, caspase-6 like activity was more sensitive to GSSG than c aspase-3 like activity. The IC50 of GSSG against caspase-3 and caspase-6-li ke activities were estimated to be 2.8 mM and 0.8 mM, respectively. Cystine but not cysteine also showed similar inhibitory effect on caspase-3-like a ctivity. The inhibitory effect of GSSG on these caspase-like activities was prevented by the addition of DTT to the assay mixture. These results sugge st that an intact disulfide portion of GSSG is required for the effective i nhibition of caspase activity.