OKADAIC ACID INHIBITS GLUCOCORTICOID-INDUCED APOPTOSIS IN T-CELL HYBRIDOMAS AT ITS LATE-STAGE

Glucocorticoids induce apoptosis in murine T cell hybridomas. It was inhibited by okadaic acid and calyculin A, potent inhibitors of protein phosphatase 1 and 2A, but not by 1-norokadaone, a structural analog of okadaic acid without phosphatase inhibitory activity. The inhibitory effect of okadaic acid was significant even when it was added 9 h after the start of the culture. Okadaic acid did not prevent either the translocation of glucocorticoid receptor from the cytoplasm to the nucleus or the induction of luciferase activity in the T cell hybridoma transfected with a plasmid containing the luciferase gene under the control of glucocorticoid response elements. These results indicate that protein dephosphorylation is an essential step for glucocorticoid-induced apoptosis in T cell hybridomas, and that the step is at the late stage of the apoptotic process. © 1993 Academic Press, Inc.