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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Endothelin receptor B-mediated induction of c-jun and AP-1 in response to shear stress in human endothelial cells.
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Endothelin receptor B-mediated induction of c-jun and AP-1 in response to shear stress in human endothelial cells.

机译:内皮素受体B介导的c-jun和AP-1响应人类内皮细胞的切应力。

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摘要

In vivo, endothelial cells are constantly exposed to shear stress by flowing blood. Short-term exposure of endothelial cells to shear stress has been shown to induce endothelin-1 release. It is currently unknown, however, whether this shear stress-dependent endothelin-1 release affects the expression and activity of transcription factors. In this study, primary cultures of human endothelial cells from the umbilical vein were exposed to laminar shear stress in a cone-and-plate viscometer. Laminar shear stress for 30 min induced a 2-fold increase in mRNA expression of c-jun , but not c-fos, in human endothelial cells. Blockade of endothelin receptor subtype B (ET B) with BQ788 prevented this shear stress-dependent induction of c-jun expression. The induction of c-jun by shear stress involved protein kinase C and endothelial NO synthase. In addition, exposure of endothelial cells to arterial laminar shear stress for 1 h increased the binding of transcription factor AP-1 to its consensus sequence by 1.7-fold in electrophoretic mobility shift assays. This induction was also mediated by an ET B-dependent pathway. Supershift analysis supports an AP-1 complex containing c-jun, but not c-fos, in human endothelial cells. In conclusion, our data suggest endothelin-1-mediated induction of c-jun expression and activation of AP-1 (possibly as a c-jun homodimer) by laminar shear stress in human endothelial cells.
机译:在体内,内皮细胞不断地通过血液流动而承受剪切应力。内皮细胞短期暴露于剪切应力下可诱导内皮素-1释放。但是,目前尚不知道这种剪切应力依赖性内皮素-1的释放是否会影响转录因子的表达和活性。在这项研究中,来自脐静脉的人内皮细胞的原代培养物在锥板粘度计中暴露于层流切应力。层流剪切应力持续30分钟,在人内皮细胞中诱导c-jun而不是c-fos的mRNA表达增加2倍。用BQ788阻断B型内皮素受体(ET B)阻止了这种剪切应力依赖性的c-jun表达诱导。剪切应力诱导的c-jun涉及蛋白激酶C和内皮一氧化氮合酶。此外,在电泳迁移率变动分析中,内皮细胞暴露于动脉层流切应力1 h使转录因子AP-1与其共有序列的结合增加了1.7倍。该诱导也由ET B依赖性途径介导。超移位分析支持在人内皮细胞中包含c-jun但不包含c-fos的AP-1复合物。总之,我们的数据表明内皮素介导的层状剪切应力在人内皮细胞中诱导c-jun表达和激活AP-1(可能是c-jun同型二聚体)。

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