Disruption of asymmetric dimethylarginine-induced RelA/P65 association with actin in endothelial cells

作者：Guo, Weikang; Zhang, Dongliang; Wang, Liyan; Zhang, Yu; Liu, Wenhu^*

来源：Acta Biochimica et Biophysica Sinica, 2013, 45(3): 229-235.

DOI：10.1093/abbs/gms120

• asymmetric dimethylarginine
• NF-kappa B
• endothelial cell
• actin-targeting drug
• VCAM-1

Asymmetric dimethylarginine (ADMA) activates nuclear factor (NF)-kappa B in endothelial cells, while actin-stabilizing or -destabilizing drugs prevent ADMA-induced activation of NF-kappa B. Here we investigated how actin-targeting drugs regulated ADMA-induced NF-kappa B activation in endothelial cells. Human umbilical vein endothelial cells were treated with ADMA for 24 h in the absence and presence of cytochalasin D or jasplakinolide. Expression levels of proteins and genes were measured by immunoblotting and reverse-transcription polymerase chain reaction, respectively. Chromatin immunoprecipitation was used to detect the binding of NF-kappa B to the vascular cell adhesion molecule 1 (VCAM-1) promoter. The association of actin with RelA/P65 was detected by immunoprecipitation. It was demonstrated that ADMA induced I kappa B alpha degradation, increased nuclear RelA/P65 translocation, and promoted the binding of NF-kappa B to the VCAM-1 promoter. Consequently, this increased the expression of VCAM-1. In parallel studies, actin-stabilizing and -destabilizing drugs decreased ADMA-induced RelA/P65 nuclear translocation, interfered with NF-kappa B binding to the VCAM-1 promoter and prevented the expression of VCAM-1. This was independent of total RelA/P65 levels and ADMA-induced I kappa B alpha degradation. Most importantly, the association of RelA/P65 with actin was increased after stimulation with ADMA, and impaired after treatment with actin-targeting drugs. In brief, actin-stabilizing or -destabilizing drugs interfere with the ADMA-induced association of RelA/P65 with actin, and consequently disrupt NF-kappa B activation.

• 出版日期2013-3
• 单位首都医科大学