12-O-tetradecanoylphorbol 13-acetate induces DNA cleavage at linker regions in mouse thymocytes.
A phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), induced the cleavage of nuclear DNA at linker regions in cultured mouse thymocytes. Similar DNA fragmentation was induced by 1-oleoyl-2-acetyl-glycerol, a synthetic diacylglycerol, but not by 4 alpha-phorbol-12,13 didecanoate. The DNA fragmentation was inhibited by 1-(5-isoquinoline-sulfonyl)-2-methyl-piperazine dihydrochloride, an inhibitor of protein kinase C, as well as actinomycin D and cycloheximide. It appears that TPA induces DNA cleavage through activation of protein kinase C and synthesis of yet unidentified protein(s). That the inhibition of DNA fragmentation was accompanied by a reduction in cell lysis suggests a causal relationship between DNA fragmentation and cell death.
Kizaki
H
H
Department of Biochemistry, School of Medicine, Keio University, Tokyo.
Shimada
H
H
Ishimura
Y
Y
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D003609:Dactinomycin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D003609:Dactinomycin; D003513:Cycloheximide; D007770:L-Lactate Dehydrogenase; D013755:Tetradecanoylphorbol Acetate