Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Alkaloids / pharmacology*
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Animals
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Apoptosis / drug effects
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Bucladesine / pharmacology
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Calcimycin / pharmacology
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Carbazoles / pharmacology
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Carcinogens
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Cells, Cultured
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DNA / chemistry
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DNA / drug effects
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DNA / metabolism
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DNA Damage / drug effects
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Dose-Response Relationship, Drug
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Indole Alkaloids
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Isoquinolines / antagonists & inhibitors
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Isoquinolines / pharmacology
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Male
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Mice
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Mice, Inbred BALB C
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Piperazines / antagonists & inhibitors
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Piperazines / pharmacology
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Protein Kinase Inhibitors
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Radiation-Sensitizing Agents
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Staurosporine
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Tetradecanoylphorbol Acetate / pharmacology
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Thymus Gland / cytology*
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Thymus Gland / drug effects*
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Time Factors
Substances
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Alkaloids
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Carbazoles
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Carcinogens
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Indole Alkaloids
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Isoquinolines
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Piperazines
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Protein Kinase Inhibitors
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Radiation-Sensitizing Agents
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Calcimycin
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Bucladesine
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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DNA
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staurosporine aglycone
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Staurosporine
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Tetradecanoylphorbol Acetate