Glutathione-S-transferase protects against oxidative injury of endothelial cell tight junctions.
Glutathione-S-transferase protects against oxidative injury of endothelial cell tight junctions.
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DOI：
10.1080/10623320701746263
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发表时间：
2007-11
期刊：
影响因子：
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通讯作者：
Ya Xu;Bin Gong;Yusong Yang;Yogesh C. Awasthi;M. Woods;P. Boor
中科院分区：
文献类型：
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作者：
Ya Xu;Bin Gong;Yusong Yang;Yogesh C. Awasthi;M. Woods;P. Boor
内皮细胞紧密连接通透性的氧化损伤参与多种血管疾病的病理生理过程。作者研究了抗氧化酶，人谷胱甘肽-S-转移酶A4-4（hGSTA 4 -4），在H（2）O（2）诱导的氧化应激下调节血管内皮细胞紧密连接主要分子表达的作用。用含hGSTA 4 -4基因的重组腺病毒载体转染血管内皮细胞系小鼠胰腺内皮细胞（MS 1）。hGSTA 4 -4在氧化应激下诱导紧密连接蛋白闭合蛋白和闭合小带（ZO）-1的表达。暴露于H（2）O后，hGSTA 4 -4表达增加与跨上皮电阻增加和occludin和ZO-1酪氨酸磷酸化降低相关（2）。此外，在hGSTA 4 -4表达细胞中，在氧化应激过程中闭合蛋白、ZO-1和F-肌动蛋白的形态解离减少。为了探索与紧密连接蛋白破坏相关的血管疾病的遗传方法，我们将相同的病毒载体引入小鼠、大鼠和兔离体血管中，发现hGSTA 4 -4在内皮细胞中强烈表达。这些结果表明，氧化应激介导的内皮细胞紧密连接的破坏可以通过hGSTA 4 -4表达而减弱。
Oxidative damage of endothelial tight junction permeability is involved in the pathophysiology of a variety of vascular diseases. The authors studied the role of the antioxidant enzyme, human glutathione-S-transferase A4-4 (hGSTA4-4), in regulating expression of major molecules of tight junction in vascular endothelial cells under oxidative stress induced by H(2)O(2). A vascular endothelial cell line, mouse pancreatic endothelial cells (MS1), was transduced with recombinant adenoviral vector containing hGSTA4-4 gene. hGSTA4-4 induced expression of tight junction proteins occludin and zonula occludens (ZO)-1 under oxidative stress. Increased hGSTA4-4 expression correlated with increased transepithelial electrical resistance and decreased tyrosine phosphorylation of occludin and ZO-1 following exposure to H(2)O(2). In addition, morphologic dissociation of occludin, ZO-1, and F-actin during oxidative stress was reduced in hGSTA4-4-expressing cells. To explore a genetic approach for vascular diseases associated with disruption of tight junction proteins, we introduced the same viral vector to blood vessels of mice, rats, and rabbits ex vivo and found strong expression of hGSTA4-4 in endothelial cells. These results demonstrate that oxidative stress mediated disruption of tight junctions in endothelial cells may be attenuated by hGSTA4-4 expression.