Glutamine Deprivation Alters Intestinal Tight Junctions via a PI3-K/Akt Mediated Pathway in Caco-2 Cells
Glutamine Deprivation Alters Intestinal Tight Junctions via a PI3-K/Akt Mediated Pathway in Caco-2 Cells
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DOI：
10.3945/jn.108.101485
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发表时间：
2009-04-01
影响因子：
4.2
通讯作者：
Neu, Josef
中科院分区：
文献类型：
--
作者：
Li, Nan;Neu, Josef
谷氨酰胺（GIP）对肠屏障功能和紧密连接（TJ）蛋白的调节很重要，但其胞内作用机制尚不清楚。本研究的目的是验证Gin在Caco-2细胞中通过磷脂酰肌醇3-激酶(PI3K)/Akt通路调节细胞间连接完整性和TJ蛋白的假设。外源性和内源性谷氨酰胺剥夺降低了上皮电阻值（TER） （P < 0.01），增加了通透性（P < 0.01）。PI3K抑制剂wortmannin和ILY294002均能阻止Gln剥夺引起的TER减少和通透性增加（P < 0.001）。Gin剥夺也导致TJ蛋白claudin-1降低（P < 0.001）。wortmannin和LY294002治疗均阻止了这种效应（P < 0.001）。剥夺Gin使磷酸化akt蛋白升高。补充杜松子酒逆转了这一效应。p85转染cacc2细胞后，其小干扰RNA的通透性和TER的降低与Gin的缺失无关。综上所示，通过PI3-3-Kinase/Akt通路，Gill调节细胞间连接完整性和TJ蛋白。中华医学杂志，39(10):711 -714,2009。
Glutamine (GIP) is important for intestinal barrier function and regulation of tight junction (TJ) proteins, but the intracellular mechanisms of action remain undefined. The purpose of this study was to test the hypothesis that Gin regulates intercellular junction integrity and TJ proteins through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in Caco-2 cells. Deprivation of exogenous and endogenous glutamine decreased transepithelial electrical resistance (TER) (P < 0.01) and increased permeability (P < 0.01). Both wortmannin and ILY294002, PI3K inhibitors, prevented the TER decrease and the permeability increase induced by Gln deprivation (P < 0.001). Gin deprivation also caused decreased TJ protein claudin-1 (P < 0.001). Both wortmannin and LY294002 treatment prevented this effect (P < 0.001). Deprivation of Gin increased phosphor-Akt protein. Gin supplementation reversed this effect. Decreased TER and increased permeability associated with Gin deprivation were not observed in small interfering RNA for p85 transfected Cacc-2 cells, In conclusion, Gill regulates intercellular junction integrity and TJ proteins through the PI3-3-Kinase/Akt pathway, J. Nutr. 139 710-714, 2009.