BIPHASIC EFFECT OF STAUROSPORINE ON THYMOCYTE APOPTOSIS

When mouse thymocytes were incubated with staurosporine at low doses ( 1-100 nM), apoptosis was induced dose- and time-dependently. Staurospo rine-induced apoptosis was dependent on macromolecular synthesis, and it was also dependent on protein phosphorylation sensitive to 1-(5-iso quinolinesulfonyl-2-methylpiperazine dihydrochloride (H-7). Whereas, s taurosporine at high doses (above 500 nM) did not induce significant D NA fragmentation, rather it inhibited the DNA fragmentation induced by 12-O-tetradecanoyl-13-acetate, A23187, and dibutyrylcyclic AMP, as H- 7 did. K252a, a derivative of staurosporine, induced apoptosis, which was inhibited by H-7, even at high doses. These results indicate that staurosporine had a biphasic effect on thymocyte apoptosis, a stimulat ory effect at low concentration, and an inhibitory effect at high conc entration. K252a had only the former action.