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 from ricin-treated U937 cells that were inhibited by glutathione disulfide (GSSG) in a dose-dependent manner, but reduced glutathione (GSH) had no effect. Interestingly, caspase-6 like activity was more sensitive to GSSG than caspase-3 like activity. The IC50 of GSSG against caspase-3 and caspase-6 like 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 activity. The inhibitory effect of GSSG on these caspase-like activities was prevented by the addition of DTT to the assay mixture. These results suggest that an intact disulfide portion of GSSG is required for the effective inhibition of caspase activity.
Sadakata
N
N
Division of Biochemistry, Faculty of Fisheries, Nagasaki University, Japan.
Oda
T
T
Komatsu
N
N
Muramatsu
T
T
D017209:Apoptosis; D053148:Caspase 3; D053178:Caspase 6; D020169:Caspases / Q000378:metabolism*; D003545:Cysteine / Q000494:pharmacology; D003553:Cystine / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology*; D019803:Glutathione Disulfide / Q000494:pharmacology*; D006801:Humans; D012276:Ricin / Q000494:pharmacology*; D020298:U937 Cells
D003553:Cystine; D012276:Ricin; C505407:CASP3 protein, human; C505514:CASP6 protein, human; D053148:Caspase 3; D053178:Caspase 6; D020169:Caspases; D005978:Glutathione; D003545:Cysteine; D019803:Glutathione Disulfide