کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5977785 | 1576258 | 2012 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Down-regulation of CREB-binding protein expression blocks thrombin-mediated endothelial activation by inhibiting acetylation of NF-κB Down-regulation of CREB-binding protein expression blocks thrombin-mediated endothelial activation by inhibiting acetylation of NF-κB](/preview/png/5977785.png)
ObjectivesCREB-binding protein (CBP) belongs to a unique class of transcription co-activators possessing histone acetyltransferase (HAT) activity. The aim of the present study was to evaluate the role of CBP in thrombin-induced endothelial activation, and also explore the underlying mechanism.MethodsLeukocyte-endothelial adhesion was calculated as the proportion of the labeled-neutrophils that adhered to ECs relative to all neutrophils applied. Levels of adhesion molecules were analyzed by real-time RT-PCR and western blot. Electrophoretic mobility shift assay and NF-κB reporter assay were performed to evaluate NF-κB activation. Acetylation of NF-κB was measured with immunoprecipitation and western blot assay. To detect the CBP-HAT activity, acetyl residues on an acetylated histone H4 was analyzed.ResultsLeukocyte-endothelial adhesion induced by thrombin was markedly attenuated in endothelial cells with CBP knockdown. The decreased adhesion was paralleled by the reduction of vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-selectin. Furthermore, CBP silencing suppressed thrombin-mediated NF-κB activation, and this inhibitory effect was associated with decreased acetylation of NF-κB and CBP-HAT activity.ConclusionsOur results indicate that CBP is involved in the regulation of endothelial activation via NF-κB-dependent pathway. Down-regulation of CBP may play a role in returning ECs from a pre-inflammatory status to a quiescent state in the pathogenesis of atherosclerosis.
Journal: International Journal of Cardiology - Volume 154, Issue 2, 26 January 2012, Pages 147-152