Study on the mechanisms of an extract of Salvia miltiorrhiza on the regulation of permeability of endothelial cells exposed to tumour necrosis factor-α
Study on the mechanisms of an extract of Salvia miltiorrhiza on the regulation of permeability of endothelial cells exposed to tumour necrosis factor-α
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DOI：
10.1211/jpp.59.7.0016
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发表时间：
2007-07-01
影响因子：
3.3
通讯作者：
Yuan, Ying-Jin
中科院分区：
文献类型：
--
作者：
Ding, Mei;Yuan, Ying-Jin
内皮细胞暴露于肿瘤坏死因子-α（TNF-α）导致内皮通透性增加，伴随着细胞-细胞粘附连接的丧失。酪氨酸磷酸酶和激酶活性在氧化剂介导的细胞连接结构丧失中的重要性已被证明。本研究的目的是确定酪氨酸磷酸化是否有助于肿瘤坏死因子-α-mediatecl破坏上皮细胞连接，以及丹参提取物（ESM）及其活性成分丹参素（DSS）和丹参酸B（Sal B）如何在维持细胞完整性方面发挥其保护作用。免疫印迹结果表明，TNF-α暴露导致连接蛋白如血管内皮钙粘蛋白和β-连环蛋白的酪氨酸磷酸化，ESM及其活性成分DSS和Sal B减弱了这种磷酸化。此外，免疫沉淀显示ESM及其活性成分阻止TNF-α处理的人脐静脉内皮细胞中β-连环蛋白从细胞骨架上解离。结果表明，TNF-α产生的生物效应至少部分通过连接蛋白磷酸酪氨酸修饰，通过增加总细胞磷酸化水平。结论：ESM及其有效成分能有效消除导致细胞磷酸化水平升高的因素，从而有助于维持上皮连接结构的完整性。
Exposure of endothelial cells to tumour necrosis factor-alpha (TNF-alpha) results in increased enclothelial permeability, accompanied by a loss of cell-cell adherence junctions. The importance of tyrosine phosphatase and kinase activity in oxidant-mediated loss of cell junction structures has been demonstrated. The purpose of this study was to determine whether tyrosine phosphorylation contributes to TNF-alpha-mediatecl disorganization of enclothelial cell junctions and how an extract of Salvia miltiorrhiza (ESM) and its active ingredients, Danshensu (DSS) and salvianolic acid B (Sal B), exert their protective effect in maintaining cell integrity. Immunoblotting results indicated that TNF-a exposure resulted in tyrosine phosphorylation of junctional proteins such as vascular enclothelial cadherin and beta-catenin, which was attenuated by ESM and its active ingredients DSS and Sal B. in addition, immunoprecipitation showed ESM and its active ingredients prevented beta-catenin disassociation from the cytoskeleton in TNF-alpha-treated human umbilical vein enclothelial cells. The results suggest that TNF-alpha produced biological effects at least partly by junctional protein phosphotyrosine modifications by increasing the total cellular phosphorylation level. It could be concluded that ESM and its active ingredients were effective at eliminating the factors leading to the rise in cellular phosphorylation, thus helping to maintain the integrity of enclothelial junction structure.