L-glutamine and L-asparagine stimulate ODC activity and proliferation in a porcine jejunal enterocyte line.
We studied the effect of L-glutamine (Gln), the principal intestinal fuel, on proliferation of a porcine jejunal cell line, IPEC-J2. In cells synchronized by serum deprivation for 4 h, Gln stimulated ornithine decarboxylase (ODC; EC 4.1.1.17) in a dose- and time-dependent manner, with maximal effects at 10 mM in 3 h (P < 0.01). Similar effects were seen for the structurally related amino acid L-asparagine and serum. The Gln effect on ODC was specific, as isosmolar mannitol, glucose, methyl-beta-D-glucoside, L-phenylalanine, ammonia, and aminoisobutyric acid were ineffective. The alanine aminotransferase inhibitor aminooxyacetate (AO) inhibited the ODC stimulation by Gln in a dose-dependent manner (half-maximal inhibitory concentration = 0.5 mM). AO was not toxic to cells, as determined by propidium iodide uptake into nuclei. In addition, Gln stimulated a twofold increase of cellular 24-h [3H]thymidine incorporation above rates of control cells bathed in standard media (P < 0.01); this effect was also blocked by AO. Gln and phorbol 12-myristate 13-acetate stimulated ODC in a synergistic manner. The Na+/H+ exchange inhibitor methylisobutyl amiloride blocked the enhancement of ODC by Gln. Gln also induced the mRNA of the immediate-early gene c-jun. Gln stimulates proliferation in a porcine jejunal cell line through a mechanism requiring transamination and intact Na+/H+ exchange. This stimulation of enterocyte proliferation by Gln suggests that therapeutic Gln administration could facilitate epithelial recovery in the injured small intestine.
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001216:Asparagine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D000518:Eflornithine / Q000494:pharmacology; D004789:Enzyme Activation; D005973:Glutamine / Q000494:pharmacology*; D007583:Jejunum / Q000166:cytology* / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013552:Swine; D013936:Thymidine / Q000378:metabolism; D000637:Transaminases / Q000037:antagonists & inhibitors
D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D017923:Sodium-Hydrogen Exchangers; D005973:Glutamine; D000625:Aminooxyacetic Acid; D001216:Asparagine; D000637:Transaminases; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D013936:Thymidine; D000518:Eflornithine