Synergic stimulation of arabinosylcytosine induced apoptosis in mouse thymocytes by cyclic AMP.
Previous studies demonstrated that arabinosylcytosine (ara-C) induced internucleosomal DNA fragmentation and cell death in mouse thymocytes and that those were inhibited by 1-(5-iso-quinoline-sulfonyl)-2-methylpiperazine hydrochloride, an inhibitor of protein kinases. In the present study, we examined the relationship between the DNA fragmentation induced by ara-C and that by agents which activate intracellular signaling and induce apoptosis in mouse thymocytes. 12-O-tetradecanoyl 13-acetate, a phorbol ester capable of activating protein kinase C or A23187, a calcium ionophore, had no effect on ara-C induced DNA fragmentation. However, ara-C induced DNA fragmentation was synergistically enhanced by cAMP and cAMP receptor agonists. Ara-C inhibited the incorporation of choline into the acid soluble and lipid fractions, and cAMP enhanced this inhibition, suggesting that ara-C metabolites interfere with membrane phospholipid metabolism, partly evoking a certain cellular signaling for apoptosis and interacting with cAMP-evoked signaling.
Azuma
Y
Y
Department of Biochemistry, Tokyo Dental College, Chiba, Japan.
Onishi
Y
Y
Mizuno
Y
Y
Kizaki
H
H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D003561:Cytarabine / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D004357:Drug Synergism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010743:Phospholipids / Q000096:biosynthesis; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007546:Isoquinolines; D010743:Phospholipids; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D003561:Cytarabine; D000001:Calcimycin; D003994:Bucladesine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000242:Cyclic AMP; D002794:Choline; D013755:Tetradecanoylphorbol Acetate