Molecular mechanisms of the synergistic induction of ornithine decarboxylase by asparagine and glucagon in primary cultured hepatocytes.
In primary cultures of adult rat hepatocytes maintained in a salts/glucose medium, a more than 100-fold increase in ornithine decarboxylase (EC 4.1.1.17) activity was caused by asparagine and glucagon in a synergistic manner. The synthesis rate of ornithine decarboxylase was determined by [35S]methionine incorporation into the enzyme protein, and the amount of ornithine decarboxylase-mRNA was measured by hybridization with a cloned rat liver ornithine decarboxylase-cDNA. The synthesis rate of ornithine decarboxylase was stimulated more than 20-fold by asparagine and glucagon together, but the amount of ornithine decarboxylase-mRNA was increased only 3-4-fold, indicating that translational stimulation was involved in the induction process. Asparagine alone stimulated the synthesis of ornithine decarboxylase without substantial effect on the amount of ornithine decarboxylase-mRNA, whereas glucagon alone increased the amount of ornithine decarboxylase-mRNA about 3-fold without a detectable change in either enzyme activity or enzyme synthesis. Asparagine, at least in part, also suppressed degradation of ornithine decarboxylase.
Kanamoto
R
R
Department of Nutrition, Jikei University School of Medicine, Tokyo, Japan.
Boyle
S M
SM
Oka
T
T
Hayashi
S
S
D000818:Animals; D001216:Asparagine / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D004790:Enzyme Induction; D005260:Female; D005934:Glucagon / Q000494:pharmacology*; D006207:Half-Life; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008813:Mice, Inbred ICR; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D012333:RNA, Messenger; D001216:Asparagine; D005934:Glucagon; D009955:Ornithine Decarboxylase