Ornithine decarboxylase activity is inhibited by the polyamine precursor amino acids at the protein stability level in Caco-2 cells

• Published in: Biochimica et biophysica acta Vol. 1723; no. 1; pp. 74 - 81
• Main Authors: Chabanon, Hervé, Aubel, Corinne, Larvaron, Pierre, Villard, Claude, Carraro, Valérie, Brachet, Patrick
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.05.2005; Elsevier
• Subjects: Antizyme; Arginine - pharmacology; Biogenic Polyamines - biosynthesis; Biological Transport - drug effects; Caco-2 Cells; Cysteine - pharmacology; Enzyme Inhibitors - pharmacology; Humans; l-Arginine; l-Methionine; Life Sciences; Methionine - pharmacology; Ornithine Decarboxylase - analysis; Ornithine Decarboxylase - genetics; Ornithine Decarboxylase Inhibitors; Polyamine; Post-translational regulation; RNA, Messenger - analysis; Spermidine - metabolism; PBS; BCA; NO; Polyamine; neAA; DTT; l-Methionine; ODC; DMEM; l-Arginine; Post-translational regulation; U; Antizyme; FCS; POST-TRANSLATIONAL REGULATION; ANTIZYME; L-METHIONINE; L-ARGININE; REGULATION POST-TRANSLATIONNELLE
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2005.01.001

High concentrations of certain amino acids are known to affect hormonal secretion, immune function, electrolyte balance or metabolic functions. However, there is a lack of knowledge regarding the molecular mechanisms responsible for these effects. We showed that, as well as spermidine transport, the activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine biosynthesis, is decreased in human colon adenocarcinoma cells, Caco-2, following a 4-h supplementation with one of the two polyamine precursor amino acids, l-arginine or l-methionine. Dose-response assays indicated that the inhibitory effect of supplemental l-methionine was stronger than that of supplemental l-arginine. However, it was transient, being even replaced by ODC induction after 8 h, whereas the inhibitory effect of l-arginine lasted for at least 8 h. Unlike l-cysteine, neither l-methionine nor l-arginine could inhibit ODC activity in a crude acellular preparation of the enzyme. The inhibition of ODC activity in cells exposed to l-methionine or l-arginine was due to a decreased abundance of ODC protein without change at the mRNA level and each of these amino acids could counteract ODC induction by a glycine supplement. Contrary to the latter, supplemental l-methionine or l-arginine induced a marked decrease in ODC half-life, concomitantly with an increase in the activity of antizyme, an ODC inhibitory protein. Thus, depending on their nature, amino acids can up- or downregulate ODC activity at the protein stability level.