Regulation of ornithine decarboxylase in 3T3 cells by putrescine and spermidine: indirect evidence for translational control.
Addition of putrescine of spermidine prevents the increase in ornithine  decarboxylase activity in cultures of 3T3 cells brought about by pituitary growth factors and results in a rapid, specific, and reversible reduction of enzyme activity in cultures previously stimulated by the growth factors. These effects are not due to polyamine toxicity and do not require other organic medium components. The amines apparently share a single carrier-mediated transport system in 3T3 cells. Methylglyoxal bis(guanylhydrazone), an inhibitor of spermidine synthesis from putrescine was found to also inhibit uptake of each amine. Studies with this drug indicate that each amine is effective without further metabolism. Since ornithine decarboxylase activity decays more rapidly in the presence of each polyamine after addition of camptothecin, the major locus of amine action appears to be in the cytoplasm. However, direct inhibition of the enzyme in vivo by assimilated amines appears to account for at most a small part of the reduction in activity, a conclusion supported by the inability to recover activity in vitro. Also, neither amine seems to act by accelerating enzyme inactivation. When amines are removed from the medium, the subsequent recovery of enzyme activity is totally prevented by trichodermin, an inhibitor of protein synthesis, but is only slightly reduced by camptothecin. It is suggested that both putrescine and spermidine reduce ornithine decarboxylase activity by selectively inhibiting translation.
D002166:Camptothecin / Q000494:pharmacology; D002262:Carboxy-Lyases / Q000378:metabolism*; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D008935:Mitoguazone / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects*; D011700:Putrescine / Q000494:pharmacology*; D013095:Spermidine / Q000494:pharmacology*; D014243:Trichodermin / Q000494:pharmacology
D014243:Trichodermin; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D008935:Mitoguazone; D013095:Spermidine; D011700:Putrescine; D002166:Camptothecin