Mechanism of Resveratrol-mediated Suppression of Tissue Factor Gene Expression
Mechanism of Resveratrol-mediated Suppression of Tissue Factor Gene Expression
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白藜芦醇介导的组织因子基因表达抑制机制
DOI：
10.1055/s-0037-1612959
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发表时间：
2002
影响因子：
6.7
通讯作者：
L. Rao
中科院分区：
文献类型：
--
作者：
U. Pendurthi;F. Meng;N. Mackman;L. Rao
组织因子（TF）是因子VII(a)的细胞表面受体，因子VII(a)与TF结合可启动凝血级联反应。血管细胞中不适当的TF在体内表达已被证明是导致与多种病理状况相关的血栓性疾病的原因，包括革兰氏阴性败血症、癌症和动脉粥样硬化。一些流行病学研究表明，适量饮用红酒对预防冠心病死亡有保护作用。最近，我们发现葡萄酒中的一种多酚类化合物白藜芦醇可以抑制内皮细胞和单核细胞中TF的表达（Pendurthi UR, Williams JT, Rao LVM）。动脉粥样硬化血栓血管生物学杂志1999；19日:419 - 426)。在本研究中，我们利用单核细胞系THP-1作为模型细胞，研究了白藜芦醇抑制单核细胞中TF表达的机制。通过Northern blot分析、凝胶迁移率转移实验和不同TF启动子结构以及其他转录调控结构的转染研究，阐明了白藜芦醇的抑制机制。结果表明，白藜芦醇能抑制脂多糖（LPS）诱导的人单核细胞和单核细胞系THP-1中TF的表达，并呈剂量依赖性。白藜芦醇对参与TF基因表达的各种转录因子与DNA的结合没有显著影响。然而，白藜芦醇抑制克隆的人TF启动子的转录。进一步的实验表明，白藜芦醇降低了κB-而不是ap -1驱动的转录活性。进一步的实验表明，白藜芦醇抑制p65的磷酸化及其反激活。综上所述，我们的研究结果表明，白藜芦醇不抑制NF-κB/Rel蛋白的激活或易位，但通过损害p65的转激活电位来抑制NF-κB/Rel依赖的转录。
Summary Tissue factor (TF) is a cell surface receptor for factor VII(a), and the binding of factor VII(a) to TF initiates the coagulation cascade. Inappropriate in vivo expression of TF in vascular cells has been shown to be responsible for thrombotic disorders associated with a variety of pathological conditions, including gram-negative sepsis, cancer and atherosclerosis. A number of epidemiological studies suggest that moderate consumption of red wine provides protective effects against coronary heart disease mortality. Recently, we have shown that resveratrol, a polyphenolic compound found in wine, inhibited the induction of TF expression in endothelial cells and mononuclear cells (Pendurthi UR, Williams JT, Rao LVM. Arterioscler Thromb Vasc Biol 1999; 19: 419-426). In the present study, we examined the mechanism by which resveratrol inhibits the expression of TF in monocytes by using a monocytic cell line, THP-1, as a model cell. Northern blot analysis, gel mobility shift assays and transfection studies with various TF promoter constructs, as well as other transcription regulatory constructs, were used to elucidate the inhibitory mechanism of resveratrol. The data show that resveratrol inhibited lipopolysaccharide (LPS)-induced expression of TF in human monocytes and monocytic cell line, THP-1 in a dose dependent manner. Resveratrol did not significantly alter the binding of various transcription factors involved in TF gene expression to DNA. However, resveratrol suppressed the transcription of cloned human TF promoter. Further experiments revealed that resveratrol reduced κB- but not AP-1-driven transcriptional activity. Additional experiments showed that resveratrol suppressed the phosphorylation of p65 and its transactivation. In summary, our results indicate that resveratrol does not inhibit the activation or translocation of NF-κB/Rel proteins but inhibits NF-κB/Rel-dependent transcription by impairing the transactivation potential of p65.
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水杨酸盐抑制脂多糖诱导的人单核细胞中组织因子基因的转录激活。
影响因子：
20.3
作者：
Oeth,P;Mackman,N
通讯作者：
Mackman,N
影响因子：
11.2
作者：
T. Hsieh;G. Juan;Z. Darżynkiewicz;Joseph M. Wu
通讯作者：
T. Hsieh;G. Juan;Z. Darżynkiewicz;Joseph M. Wu
影响因子：
5.8
作者：
Wadsworth, TL;Koop, DR
通讯作者：
Koop, DR
影响因子：
15.9
作者：
MCNAMARA, CA;SAREMBOCK, IJ;OWENS, GK
通讯作者：
OWENS, GK
DOI：
10.1073/pnas.86.8.2839
发表时间：
1989-04-01
影响因子：
11.1
作者：
WILCOX, JN;SMITH, KM;GORDON, D
通讯作者：
GORDON, D