Inducible nitric oxide regulates intestinal glutamine assimilation during chronic intestinal inflammation
Inducible nitric oxide regulates intestinal glutamine assimilation during chronic intestinal inflammation
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DOI：
10.1016/j.niox.2014.12.006
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发表时间：
2015-01-30
影响因子：
3.9
通讯作者：
Sundaram, Uma
中科院分区：
文献类型：
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作者：
Arthur, Subha;Sundaram, Uma
为了促进谷氨酰胺的同化，在兔小肠中存在不同的Na依赖性谷氨酰胺吸收途径，特别是绒毛中的BOAT 1和隐窝细胞刷状缘膜中的SN 2。此外，两者在慢性发炎的肠道中受到独特的调节。BOAT 1被抑制，继发于刷状缘膜（BBM）共转运蛋白数量的减少，而SN 2被刺激，继发于对谷氨酰胺的亲和力增加。这些独特的变化是可逆的治疗与广谱免疫调节剂，如糖皮质激素。然而，是否诱导型一氧化氮（iNO），已知是在慢性炎症肠粘膜升高，可能是负责这些协同转运蛋白的改变是未知的。在本研究中，用选择性iNO合酶抑制剂L-NIL治疗慢性炎症兔，逆转了绒毛中BOAT 1的抑制和隐窝细胞中SN 2的刺激。在刷状缘膜中的共转运蛋白水平，抑制iNO的产生通过恢复共转运蛋白的数量来逆转绒毛BOAT 1的抑制，而通过恢复其对谷氨酰胺的亲和力来逆转隐窝SN 2的刺激。BBM蛋白的Western印迹分析也证实了动力学研究。因此，L-NIL治疗恢复了慢性炎症肠的肠细胞中独特改变的Na-谷氨酰胺共转运蛋白。所有这些数据表明，iNO的功能作为上游免疫调节剂直接调节谷氨酰胺同化过程中慢性肠道炎症。(C)由Elsevier Inc.出版。
To facilitate assimilation of glutamine, different Na-dependent glutamine absorptive pathways are present in the rabbit small intestine, specifically BOAT1 in villus and SN2 in crypt cell brush border membrane. Further, both are uniquely regulated in the chronically inflamed intestine. BOAT1 is inhibited secondary to reduced number of brush border membrane (BBM) co-transporters while SN2 is stimulated secondary to an increased affinity for glutamine. These unique changes are reversible by treatment with a broad spectrum immune modulator such as glucocorticoids. However, whether inducible nitric oxide (iNO),, known to be elevated in the mucosa of the chronically inflamed intestine, may be responsible for these co-transporter alterations is not known. In the present study, treatment of chronically inflamed rabbits with L-NIL, a selective inhibitor of iNO synthase, reversed the inhibition of BOAT1 in villus and the stimulation of SN2 in crypt cells. At the level of the co-transporter in the brush border membrane, inhibition of iNO production reversed the inhibition of villus BOAT1 by restoring the co-transporter numbers while the stimulation of crypt SN2 was reversed back to normal by restoring its affinity for glutamine. Western blot analyses of BBM proteins also confirmed the kinetic studies. Thus, L-NIL treatment restores the uniquely altered Na-glutamine co-transporters in the enterocytes of chronically inflamed intestine. All these data indicate that iNO functions as an upstream immune modulator directly regulating glutamine assimilation during chronic intestinal inflammation. (C) 2014 Published by Elsevier Inc.