Stimulation of ornithine decarboxylase synthesis and its control by polyamines in regenerating rat liver and cultured rat hepatoma cells.
Ornithine decarboxylase has been induced in log phase hepatoma cells grown in suspension culture. Induction with N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate produced a 4-fold increase in enzyme activity by 3 hours which was followed by a return to base levels by 6 hours. Induction  with dexamethasone, a potent synthetic glucocorticoid, exhibited a slow steady rate of increase in enzyme activity, reaching a plateau level of approximately 5- to 6-fold stimulation by about 12 hours. Induced cell and regenerating rat liver ornithine decarboxylase were shown to be indistinguishable by titration with antibody monospecific to the latter and by heat stability. L-[14C]Leucine incorporation into immunoprecipitable enzyme protein after induction in vitro or partial hepatectomy showed an increase which, when coupled with the increase in enzymatic activity, indicated de novo synthesis of enzyme protein. Physiological concentrations of the naturally occurring polyamines, spermidine and spermine, abolish cyclic AMP induction whereas they have no effect on dexamethasone induction. Both inductions were abolished by cycloheximide; in contrast, inhibition by actinomycin D was complete for dexamethasone induction and only partial with respect to cyclic AMP induction. The different time pattern of induction seen with cyclic AMP and dexamethasone, the partial inhibition of the cyclic AMP induction seen with actinomycin D, as well as the absence of inhibition of the dexamethasone induction by polyamines, indicate that these inducers might affect different aspects of the control of the same enzyme.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002262:Carboxy-Lyases / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004355:Drug Stability; D004790:Enzyme Induction / Q000187:drug effects; D006358:Hot Temperature; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008113:Liver Neoplasms; D008115:Liver Regeneration / Q000187:drug effects*; D009374:Neoplasms, Experimental / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011073:Polyamines / Q000494:pharmacology*; D011233:Precipitin Tests; D051381:Rats; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013997:Time Factors
D011073:Polyamines; D003609:Dactinomycin; D013096:Spermine; D003994:Bucladesine; D003513:Cycloheximide; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D013095:Spermidine