L-GLUTAMINE AND L-ASPARAGINE STIMULATE ODC ACTIVITY AND PROLIFERATION IN A PORCINE JEJUNAL ENTEROCYTE LINE
L-GLUTAMINE AND L-ASPARAGINE STIMULATE ODC ACTIVITY AND PROLIFERATION IN A PORCINE JEJUNAL ENTEROCYTE LINE
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DOI：
10.1152/ajpgi.1995.269.4.g591
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发表时间：
1995-10-01
影响因子：
4.5
通讯作者：
RHOADS, JM
中科院分区：
文献类型：
--
作者：
KANDIL, HM;ARGENZIO, RA;RHOADS, JM
我们研究了L-谷氨酰胺（Gln），主要的肠道燃料，对猪空肠细胞系，IPEC-J2增殖的影响。在通过血清剥夺4小时同步化的细胞中，Gln以剂量和时间依赖性方式刺激鸟氨酸脱羧酶（ODC; EC 4.1.1.17），在3小时内在10 mM下具有最大效应（P < 0.01）。在结构相关的氨基酸L-天冬酰胺和血清中观察到类似的作用。Gln对ODC的影响是特异性的，因为等渗甘露醇、葡萄糖、甲基-β-D-葡萄糖苷、L-苯丙氨酸、氨和氨基异丁酸无效。丙氨酸氨基转移酶抑制剂氨氧基乙酸（AO）抑制谷氨酰胺的ODC刺激的剂量依赖性的方式（半最大抑制浓度= 0.5 mM）。AO是没有毒性的细胞，碘化丙啶摄取到细胞核。此外，Gin刺激细胞24-h [H-3]胸苷掺入率比标准培养基中的对照细胞高两倍（P < 0.01）; AO也阻断了这种作用。谷氨酰胺和佛波醇12-肉豆蔻酸酯13-乙酸酯以协同方式刺激ODC。Na+/H+交换抑制剂甲基异丁基阿米洛利（methylisobutylamiloride）可阻断Gln对ODC的增强作用。谷氨酰胺还诱导即时早期基因c-jun的mRNA。谷氨酰胺通过需要转氨作用和完整的Na+/H+交换的机制刺激猪空肠细胞系的增殖。谷氨酰胺对肠上皮细胞增殖的刺激表明，治疗性谷氨酰胺给药可促进受损小肠上皮细胞的恢复。
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, Gin stimulated a twofold increase of cellular 24-h [H-3]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.