Programmed cell death (apoptosis) is induced rapidly and with positive cooperativity by activation of cyclic adenosine monophosphate-kinase I in a myeloid leukemia cell line.
Programmed death (apoptosis) of the rat myelocytic leukemic cell line IPC-81 was triggered by cyclic adenosine monophosphate (cAMP) analogs or by agents (cholera toxin, prostaglandins) increasing the endogenous cAMP level. The induction of cell death by cholera toxin was preceded by increased activation of cAMP-kinase. Cell lysis started already 5 hr after cAMP challenge and was preceded by internucleosomal DNA fragmentation and morphological changes characteristic of apoptosis. The cell suicide could be prevented by inhibitors of macromolecular synthesis. cAMP analogs induced cell death in a positively cooperative manner (apparent Hill coefficient of 2.9), indicating that triggering of the apoptotic process was under stringent control. There was a strong synergism between cAMP analogs complementing each other in the activation of cAMP-dependent protein kinase I (cAKI). No such synergism was noted for analogs complementing each other in the activation of cAKII. It is concluded that apoptosis can be induced solely by activation of cAKI. The IPC-81 cells expressed about four times more cAKI than cAKII. The expression of cAK subunits, on the protein and mRNA levels, was only minimally affected by cholera toxin treatment.
Lanotte
M
M
INSERM U301, Centre Hayem, Hôpital St-Louis, Paris, France.
Riviere
J B
JB
Hermouet
S
S
Houge
G
G
Vintermyr
O K
OK
Gjertsen
B T
BT
Døskeland
S O
SO
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology*; D004249:DNA Damage; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007527:Isoenzymes / Q000502:physiology; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D009697:Nucleolus Organizer Region / Q000378:metabolism; D011494:Protein Kinases / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D012333:RNA, Messenger; D002772:Cholera Toxin; D000242:Cyclic AMP; D011494:Protein Kinases