L-glutamine and L-asparagine stimulate ODC activity and proliferation in a porcine jejunal enterocyte line

Abstract

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.

Important roles for the arginine family of amino acids in swine nutrition and production

“…In addition, this amino acid increases expression of ornithine decarboxylase (ODC; Kandil et al, 1995), a key enzyme for the synthesis of polyamines that function to stimulate DNA and protein synthesis (Flynn et al, 2002). Further, glutamine is required for the synthesis of N-acetylglucosamine-6-phosphate, a common substrate for the synthesis of glycoproteins that are particularly rich in intestinal mucosal cells Wang et al, 2006Wang et al, , 2007.…”

Glutamine Stimulates Argininosuccinate Synthetase Gene Expression through Cytosolic O-Glycosylation of Sp1 in Caco-2 Cells

“…Among amino acids, glutamine, which is the most abundant circulating amino acid, stimulates or inhibits the expression of various genes. This includes (i) intracellular proteins such as transcription factors (3,4), constitutive proteins of the cytoskeleton (5,6) and of the extracellular matrix (7), heat shock proteins (8) or metabolic enzymes (9,10); (ii) membrane proteins such as the transport system (11); and (iii) secreted proteins such as acute phase proteins (12), cytokines (13,14), and growth factor (15). However, the molecular mechanism(s) involved in the glutamine effect is not totally understood and may depend on the cell type studied.…”

Efeito da adição de agentes tróficos na dieta de leitões desmamados sobre a estrutura e ultraestrutura do intestino delgado e sobre o desempenho

“…(Kandil et al, 1995), a qual aumenta a produção de poliaminas que atuam na maturação e regeneração da mucosa intestinal (Wang et al, 1998), ou pela diminuição da morte celular (Chow e Zhang, 1998).…”