Cyclooxygenase pathway mediates the inhibition of Na-glutamine co-transporter B0AT1 in rabbit villus cells during chronic intestinal inflammation.
Cyclooxygenase pathway mediates the inhibition of Na-glutamine co-transporter B0AT1 in rabbit villus cells during chronic intestinal inflammation.
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DOI：
10.1371/journal.pone.0203552
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Sundaram U
中科院分区：
文献类型：
--
作者：
Arthur S;Singh S;Sundaram U
在哺乳动物肠道中，吸收绒毛细胞的谷氨酰胺同化是通过na -谷氨酰胺共运输介导的，特别是通过B0AT1。在兔慢性肠道炎症模型中，B0AT1的抑制继发于刷状边界膜（BBM）共转运蛋白数量的减少。这种抑制可以通过糖皮质激素等广谱免疫调节剂治疗逆转，这表明免疫炎症介质可能在慢性肠道炎症期间调节B0AT1。花生四烯酸（AA）代谢物（AAM）在慢性肠道炎症期间增加。然而，AAM是否在慢性肠道炎症中调控B0AT1尚不清楚。用ATK治疗家兔，阻止AAM的释放逆转了对B0AT1的抑制。AAM是环氧化酶（COX）和/或脂氧化酶（LOX）途径的产物。吡罗昔康抑制COX，从而减少慢性炎症肠道中前列腺素的形成，逆转了对B0AT1的抑制，使其恢复到正常水平。相反，MK886抑制LOX，从而减少慢性肠炎期间白三烯的形成，不影响B0AT1的抑制。动力学研究表明，ATK或吡罗西康对B0AT1的恢复机制是次于BBM共转运蛋白数量的恢复。Western Blot分析也显示BBM B0AT1共转运蛋白数量的恢复。综上所述，本研究表明，在慢性炎症肠道中，绒毛细胞中由B0AT1介导的na -谷氨酰胺共运输受前列腺素而非白三烯调节。
In the mammalian intestine, glutamine assimilation by the absorptive villus cells is mediated by Na-glutamine co-transport, specifically by B0AT1. In a rabbit model of chronic intestinal inflammation, B0AT1 is inhibited secondary to a decrease in the number of co-transporters in the brush border membrane (BBM). This inhibition can be reversed by treatment with a broad-spectrum immune modulator such as glucocorticoid suggesting that immune inflammatory mediators may regulate B0AT1 during chronic intestinal inflammation. Arachidonic acid (AA) metabolites (AAM) are increased during chronic intestinal inflammation. However, whether AAM may regulate B0AT1 during chronic intestinal inflammation is unknown. Treatment of rabbits with ATK, to prevent the release of AAM reversed the inhibition of B0AT1. AAM are products of cyclooxygenase (COX) and/or lipoxygenase (LOX) pathways. Inhibition of COX with piroxicam, therefore reduction of prostaglandin formation in the chronically inflamed intestine, reversed the inhibition of B0AT1 to its normal levels. In contrast, inhibition of LOX with MK886, thus reduction of leukotriene formation during chronic enteritis, did not affect the inhibition of B0AT1. Kinetic studies showed that the mechanism of restoration of B0AT1 by ATK or piroxicam was secondary to the restoration of BBM co-transporter numbers. Western Blot analysis also demonstrated restoration of BBM B0AT1 co-transporter numbers. In conclusion, this study demonstrates that Na-glutamine co-transport mediated by B0AT1 in villus cells is regulated by prostaglandins rather than leukotrienes in the chronically inflamed intestine.
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影响因子：
4.2
作者：
Boelens, PG;Houdijk, APJ;Van Leeuwen, PAM
通讯作者：
Van Leeuwen, PAM
影响因子：
7.1
作者：
Calder, Philip C.
通讯作者：
Calder, Philip C.
影响因子：
4.9
作者：
Arthur, Subha;Saha, Prosenjit;Sundaram, Uma
通讯作者：
Sundaram, Uma
影响因子：
4.2
作者：
Bode, BP
通讯作者：
Bode, BP
DOI：
10.1073/pnas.71.10.3824
发表时间：
1974-01-01
影响因子：
11.1
作者：
HAMBERG, M;SVENSSON, J;SAMUELSSON, B
通讯作者：
SAMUELSSON, B