Final checkpoint in the drug-promoted and poliovirus-promoted apoptosis is under post-translational control by growth factors.
The treatment of HeLa subline (HeLa-B) cells with cycloheximide or Actinomycin D resulted in a rapid (approximately 1.5 h and approximately 2.5 h, respectively) development of morphological and biochemical signs of apoptosis. The addition of fetal bovine serum to the cycloheximide-treated or Actinomycin D-treated cells suppressed the apoptotic reaction, as evidenced by the postponement of the DNA fragmentation for at least 9 and 5 h, respectively. A similar suppressive effect was observed upon the serum addition to cells undergoing abortive infection with poliovirus, which died of apoptosis in the absence of the serum. The serum appeared to exert its anti-apoptotic effect without any appreciable lag and even immediately blocked further progress of ongoing DNA fragmentation. The epidermal growth factor also suppressed, although less efficiently and more transiently, the apoptotic reaction promoted by the metabolic inhibitors. It is concluded that growth factors may affect, without modulating either transcription or translation, the balance of pro-apoptotic and anti-apoptotic activities at a final checkpoint, just preceding the irreversible effector step of apoptosis.
Tolskaya
E A
EA
M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region, Russia.
Romanova
L I
LI
Kolesnikova
M S
MS
Ivannikova
T A
TA
Agol
V I
VI
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D001798:Blood Proteins / Q000494:pharmacology*; D016895:Culture Media, Serum-Free; D003513:Cycloheximide / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006367:HeLa Cells / Q000502:physiology* / Q000821:virology; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D011051:Poliomyelitis / Q000503:physiopathology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*
D001798:Blood Proteins; D016895:Culture Media, Serum-Free; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D003513:Cycloheximide