Mechanism of Na-K-ATPase Inhibition by PGE2 in Intestinal Epithelial Cells.
Mechanism of Na-K-ATPase Inhibition by PGE2 in Intestinal Epithelial Cells.
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DOI：
10.3390/cells10040752
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发表时间：
2021-03-29
期刊：
影响因子：
6
通讯作者：
Sundaram U
中科院分区：
文献类型：
--
作者：
Nepal N;Arthur S;Haynes J;Palaniappan B;Sundaram U
绒毛细胞吸收营养物质的主要途径是通过位于刷状缘膜的钠依赖的营养共转运蛋白(BBM)。这些二次活跃的共转运过程需要Na-K-ATPase提供的良好的跨细胞钠梯度。在慢性肠炎中，必需营养物质的吸收不良部分是由于绒毛Na-K-ATPase活性受到抑制，这种抑制是由特定的免疫炎症介质介导的，已知炎症介质在炎症的粘膜中升高。然而，绒毛中营养物质吸收不良的特异性介质前列腺素E2(PGE2)如何介导Na-K-ATPase的抑制尚不清楚。因此，本研究旨在探讨前列腺素E_2对绒毛细胞Na-K-ATPase的影响及其作用机制。体外培养的IEC-18细胞经PGE2处理后，Na-K-ATPase活性显著降低，细胞内cAMP水平显著升高。CAMP类似物8-溴-cAMP处理模拟PGE_2介导的Na-K-ATPase活性，而RP-cAMP(PKA抑制剂)则逆转同样的作用。抑制前列腺素E_2的作用机制是通过抑制Na-K-ATPaseα1和β1亚单位基因的转录而实现的，而这一作用可被RP-cAMP预处理所逆转。因此，PGE2介导的PKA途径的激活在体外介导了对Na-K-ATPase活性的转录抑制。
The primary means of intestinal absorption of nutrients by villus cells is via Na-dependent nutrient co-transporters located in the brush border membrane (BBM). These secondary active co-transport processes require a favorable transcellular Na gradient that is provided by Na-K-ATPase. In chronic enteritis, malabsorption of essential nutrients is partially due to inhibition of villus Na-K-ATPase activity mediated by specific immune inflammatory mediators that are known to be elevated in the inflamed mucosa. However, how Prostaglandin E2 (PGE2), a specific mediator of nutrient malabsorption in the villus BBM, may mediate the inhibition of Na-K-ATPase is not known. Therefore, this study aimed to determine the effect of PGE2 on Na-K-ATPase in villus cells and define its mechanism of action. In vitro, in IEC-18 cells, PGE2 treatment significantly reduced Na-K-ATPase activity, accompanied by a significant increase in the intracellular levels of cyclic Adenosine Monophosphate (cAMP). The treatment with cAMP analog 8-Bromo-cAMP mimicked the PGE2-mediated effect on Na-K-ATPase activity, while Rp-cAMP (PKA inhibitor) pretreatment reversed the same. The mechanism of inhibition of PGE2 was secondary to a transcriptional reduction in the Na-K-ATPase α1 and β1 subunit genes, which was reversed by the Rp-cAMP pretreatment. Thus, the PGE2-mediated activation of the PKA pathway mediates the transcriptional inhibition of Na-K-ATPase activity in vitro.
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影响因子：
3.9
作者：
Blanco, G;Sánchez, G;Mercer, RW
通讯作者：
Mercer, RW
影响因子：
3.7
作者：
Arthur S;Singh S;Sundaram U
通讯作者：
Sundaram U
DOI：
10.1111/j.1439-0442.1997.tb01129.x
发表时间：
1997-09-01
期刊：
JOURNAL OF VETERINARY MEDICINE SERIES A-PHYSIOLOGY PATHOLOGY CLINICAL MEDICINE
影响因子：
--
作者：
Hyun, HS;Arai, S;Kato, S
通讯作者：
Kato, S
DOI：
10.1016/s1388-1981(99)00164-x
发表时间：
2000-01-17
影响因子：
4.8
作者：
Abramovitz, M;Adam, M;Metters, KM
通讯作者：
Metters, KM
影响因子：
4.9
作者：
Arthur, Subha;Saha, Prosenjit;Sundaram, Uma
通讯作者：
Sundaram, Uma