Molecular mechanism for the regulation of hepatic ornithine decarboxylase.
A single injection of thioacetamide into starved rats induced a 40- to 100-fold increase in hepatic ODC activity. However, immunotitratable ODC protein increased by only 5-fold because of the presence of significant amounts of inactive ODC protein in the liver of untreated starved rats. Polysomal ODC-mRNA activity also increased only 5-fold, a significant amount being present in control liver. Furthermore, the peak of polysomal ODC-mRNA activity preceded that of ODC activity or ODC protein by several hours. These results indicate that the enzyme induction is due not only to increase in polysomal ODC-mRNA activity, but also to some translational and/or post-translational regulation. Exogenously administered diamines or polyamines cause rapid decay of ODC activity and induce antizyme that binds to ODC and inactivates it. Another protein factor, antizyme inhibitor, was found in the liver of thioacetamide-treated or protein-fed rats. Antizyme inhibitor binds to antizyme and reactivates ODC in the ODC-antizyme complex. A small, but significant, amount of antizyme was found in the liver of starved rats. Only small amounts of ODC-antizyme complex were detected in rat liver and cultured hepatocytes, even during the period of rapid ODC decay caused by exogenously added diamines. On the other hand, the complex was present in HTC cells and more especially in ODC-stabilized HMOA cells, even under physiological conditions. On addition of 10(-2) M putrescine, the amount of complex first increased and then decreased in both types of cells. Decay of total ODC activity (free plus complexed ODC) was more rapid with putrescine than with cycloheximide. These results suggest that antizyme plays an essential role in the degradation of ODC by a catalytic effect both in the presence and absence of exogenous putrescine and that antizyme inhibitor stabilizes ODC by removing antizyme.
D000818:Animals; D002478:Cells, Cultured; D004044:Dietary Proteins / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000201:enzymology*; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011132:Polyribosomes / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013853:Thioacetamide / Q000494:pharmacology
D004044:Dietary Proteins; D065108:Ornithine Decarboxylase Inhibitors; D011506:Proteins; D012333:RNA, Messenger; C031017:ornithine decarboxylase antizyme; D013853:Thioacetamide; D009955:Ornithine Decarboxylase