Peroxynitrite inhibits the activity of ornithine decarboxylase.
Polyamines are required during cell proliferation, whereas NO has anti-proliferative properties. Ornithine decarboxylase (ODC) is a critical enzyme for the synthesis of polyamines. We tested the hypothesis that the modification of ODC by peroxynitrite (OONO-), a short-lived free radical formed from NO and superoxide produces a fall in ODC activity, and therefore polyamine synthesis and cell proliferation. The treatment of a rat recombinant ODC (rODC) with OONO- resulted in a dose-dependent inhibition of rODC activity with an IC50 of approximately 100 microM. A Western blot employing a specific antibody to nitrotyrosine revealed a dose-dependent nitration of rODC tyrosine residues. When intact IEC-6 cells were treated with ONOO-, ODC activity decreased by 49%. These data suggest a correlation between ODC activity and nitration, and a possible mechanism by which NO synthesis may modulate polyamine synthesis.
Department of Physiology, Brody School of Medicine East Carolina University, Greenville, NC 27858, U.SA.
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D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D009566:Nitrates / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
D004791:Enzyme Inhibitors; D009566:Nitrates; D065108:Ornithine Decarboxylase Inhibitors; D016877:Oxidants; D011994:Recombinant Proteins; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D009955:Ornithine Decarboxylase