Involvement of antizyme in stabilization of ornithine decarboxylase caused by inhibitors of polyamine synthesis.
Contrary to previous findings, ornithine decarboxylase (ODC) was stabilized by treatment of cells with DL-alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ODC. Both this inhibitor and cyclohexylamine, a spermidine synthase inhibitor known to stabilize ODC, caused decreases in the antizyme/ODC ratio by increasing ODC content and conversely decreasing antizyme content. The relationship between cellular polyamine levels and antizyme content indicated that spermidine is the most important polyamine for antizyme induction. These results suggest that antizyme is involved in the mechanism underlying the stabilization of ODC by inhibitors of polyamine synthesis and support the hypothesis that cellular polyamines regulate ODC degradation via antizyme.
Murakami
Y
Y
Department of Nutrition, Jikei University School of Medicine, Tokyo, Japan.
Nishiyama
M
M
Hayashi
S
S
D000818:Animals; D002460:Cell Line; D003514:Cyclohexylamines / Q000494:pharmacology; D000518:Eflornithine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004795:Enzyme Stability; D006801:Humans; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000096:biosynthesis* / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins; D013095:Spermidine / Q000494:pharmacology
D003514:Cyclohexylamines; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011506:Proteins; C031017:ornithine decarboxylase antizyme; D009955:Ornithine Decarboxylase; D013095:Spermidine; D000518:Eflornithine