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. Staurosporine-induced apoptosis was dependent on macromolecular synthesis, and it was also dependent on protein phosphorylation sensitive to 1-(5-isoquinolinesulfonyl-2-methylpiperazine dihydrochloride (H-7). Whereas, staurosporine at high doses (above 500 nM) did not induce significant DNA 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 stimulatory effect at low concentration, and an inhibitory effect at high concentration. K252a had only the former action.
Suzuki
K
K
Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan.
Azuma
Y
Y
Onishi
Y
Y
Kizaki
H
H
Ishimura
Y
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002273:Carcinogens; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D026121:Indole Alkaloids; D007546:Isoquinolines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011838:Radiation-Sensitizing Agents; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects*; D013997:Time Factors
D000470:Alkaloids; D002227:Carbazoles; D002273:Carcinogens; D026121:Indole Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011838:Radiation-Sensitizing Agents; D000001:Calcimycin; D003994:Bucladesine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004247:DNA; C049985:staurosporine aglycone; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate