Selective stimulation of brush border glutamine transport in the tumor-bearing rat.
Selective stimulation of brush border glutamine transport in the tumor-bearing rat.
复制标题
选择性刺激荷瘤大鼠刷状缘谷氨酰胺转运。
DOI：
10.1016/0022-4804(91)90208-4
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Souba,WW
中科院分区：
文献类型：
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作者：
Salloum,RM;Copeland3rd,EM;Bland,KI;Souba,WW
荷瘤大鼠（TBR）肠内循环谷氨酰胺穿过基底外膜的提取减少。本研究旨在探讨进行性恶性肿瘤生长对刷状边界谷氨酰胺运输的影响，以进一步了解荷瘤大鼠肠道谷氨酰胺代谢的适应性/调节性变化。将Fischer 344大鼠（225±5 g）植入纤维肉瘤细胞，并在植入后肿瘤占总体重的7%、20%和29%的不同时间点进行研究。在整个研究过程中，对照大鼠和荷瘤大鼠成对进食。采用镁聚集/差速离心法制备空肠刷状边界膜泡（BBMVs），并采用Millipore过滤技术测定BBMVs对放射性标记的谷氨酰胺、亮氨酸、丙氨酸和葡萄糖的转运。bbmv在碱性磷酸酶中富集了15倍，表明刷边泡的纯度。所有底物的吸收都发生在渗透活性空间，表现出过调，并且具有相似的1小时平衡值。无论肿瘤大小如何，bbmv对所有荷瘤大鼠的谷氨酰胺摄取率均显著高于对照组。转运活性的增加不是由于载流子亲和力的改变，而是由于最大转运速度的增加。小肿瘤大鼠（体重的7%）的vmax为431±40摩尔/mg蛋白/10秒，而对照组为259±30摩尔（P< 0.01）。与此形成鲜明对比的是，TBR减少了bbmv中丙氨酸的平均转运（TBR组为31±3摩尔/mg蛋白/10秒，对照组为23±2摩尔/mg蛋白/10秒，P< 0.05）。对照组和TBR之间葡萄糖和亮氨酸转运无显著差异。结果表明，在该肿瘤模型中发生的刷状边界运输上调可能是谷氨酰胺特异性的，表明谷氨酰胺具有较高的细胞优先权和需求。这种在荷瘤动物的灌木边界运输活动中的适应性调节以前没有被描述过。
Intestinal extraction of circulating glutamine across the basolateral membrane is diminished in the tumor-bearing rat (TBR). This study was designed to investigate the effects of progressive malignant growth on brush border glutamine transport in order to gain further insight into the adaptive/regulatory changes in intestinal glutamine metabolism that occur in the tumor-bearing rat. Fischer 344 rats (225 ± 5 g) were implanted with fibrosarcoma cells and were studied at various time points after implantation when the tumors comprised 7%, 20%, and 29% of total body weight. Control and tumor-bearing rats were pair-fed throughout the study. Jejunal brush border membrane vesicles (BBMVs) were prepared by magnesium aggregation/differential centrifugation and transport of radioactively labeledl-glutamine,l-leucine,l-alanine, andd-glucose by BBMVs was measured using a Millipore filtration technique. BBMVs were enriched 15-fold in alkaline phosphatase, indicating brush border vesicle purity. Uptake of all substrates occurred into an osmotically active space, exhibited overshoots, and had similar 1-hr equilibrium values. The rate of glutamine uptake by BBMVs from all tumor-bearing rats was significantly greater than controls, regardless of tumor size. The increase in transport activity was not due to a change in carrier affinity but rather to an increase in maximal transport velocity. In rats with small tumors (7% of body weight), theVmaxwas 431 ± 40 pmole/mg protein/10 sec compared to 259 ± 30 in control animals (P< 0.01). In marked contrast, the mean transport of alanine was diminished in BBMVs from TBR (31 ± 3 pmole/mg protein/10 sec in TBR vs 23 ± 2 in controls,P< 0.05). There was no significant difference in glucose and leucine transport between control and TBR. The results suggest that the upregulation in brush border transport that occurs in this tumor model may be specific for glutamine, indicating the high cellular priority and requirement for glutamine. Such adaptive regulation in brush border transport activity in tumor-bearing animals has not been previously described.