Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism
Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism
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DOI：
10.1152/ajpgi.00202.2007
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发表时间：
2008-04-01
影响因子：
4.5
通讯作者：
Rao, R. K.
中科院分区：
文献类型：
--
作者：
Seth, A.;Yan, Fang;Rao, R. K.
益生菌促进肠上皮完整性，减少感染和腹泻。我们评估了鼠李糖乳杆菌GG产生的可溶性蛋白（p40和p75）对过氧化氢诱导的Caco-2细胞单层紧密连接和屏障功能破坏的影响。用p40或p75预处理细胞单层以时间和剂量依赖性方式减弱过氧化氢诱导的跨上皮电阻降低和菊粉渗透性增加。p40和p75还阻止过氧化氢诱导的occludin、ZO-1、E-钙粘蛋白和β-连环蛋白从细胞间连接处的重新分布以及它们从洗涤剂不溶性部分的解离。p40和p75均诱导PKC β I和PKC β I的膜转位迅速增加。PKC抑制剂Ro-32-0432可抑制过氧化氢诱导的菊粉渗透性减弱和p40和p75引起的紧密连接蛋白的再分布。p40和p75也迅速增加洗涤剂不溶性组分中磷酸化ERK 1/2的水平。U 0126（MAP激酶抑制剂）减弱了p40和p75介导的过氧化氢诱导的紧密连接破坏和菊粉渗透性的降低。这些研究表明，益生菌分泌蛋白保护肠上皮细胞紧密连接和屏障功能从过氧化氢诱导的损伤的PKC和MAP激酶依赖性机制。
Probiotics promote intestinal epithelial integrity and reduce infection and diarrhea. We evaluated the effect of Lactobacillus rhamnosus GG-produced soluble proteins (p40 and p75) on the hydrogen peroxide-induced disruption of tight junctions and barrier function in Caco-2 cell monolayers. Pretreatment of cell monolayers with p40 or p75 attenuated the hydrogen peroxide-induced decrease in transepithelial resistance and increase in inulin permeability in a time- and dose-dependent manner. p40 and p75 also prevented hydrogen peroxide-induced redistribution of occludin, ZO-1, E-cadherin, and beta-catenin from the intercellular junctions and their dissociation from the detergent-insoluble fractions. Both p40 and p75 induced a rapid increase in the membrane translocation of PKC beta I and PKC epsilon. The attenuation of hydrogen peroxide-induced inulin permeability and redistribution of tight junction proteins by p40 and p75 was abrogated by Ro-32-0432, a PKC inhibitor. p40 and p75 also rapidly increased the levels of phospho-ERK1/2 in the detergent-insoluble fractions. U0126 (a MAP kinase inhibitor) attenuated the p40- and p75-mediated reduction of hydrogen peroxide-induced tight junction disruption and inulin permeability. These studies demonstrate that probiotic-secretory proteins protect the intestinal epithelial tight junctions and the barrier function from hydrogen peroxide-induced insult by a PKC- and MAP kinase-dependent mechanism.