STIMULATION OF TRANSCRIPTION FACTORS NF-KAPPA-B AND AP1 IN ENDOTHELIAL-CELLS SUBJECTED TO SHEAR-STRESS

STIMULATION OF TRANSCRIPTION FACTORS NF-KAPPA-B AND AP1 IN ENDOTHELIAL-CELLS SUBJECTED TO SHEAR-STRESS
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DOI:
10.1006/bbrc.1994.1794
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发表时间:
1994-06-15
影响因子:
3.1
通讯作者:
DAVIES, PF
DAVIES, PF
中科院分区:
生物学4区
文献类型:
--
作者:
LAN, QX;MERCURIUS, KO;DAVIES, PF

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血流动力学剪切力影响与动脉舒张、促/抗凝和生长控制相关的几个重要内皮基因;然而,监管途径仍不清楚。在这里,我们证明了在内皮细胞暴露于层流中单向剪切应力后,核因子κ B (NF κ B)(转录因子Rel家族的成员)和核因子激活蛋白-1 (AP-1)的DNA结合活性受到刺激。在30分钟内刺激NF κ B结合,在1小时达到并维持最大水平。核提取物与NF κ B p65亚基抗体预孵育可抑制DNA结合活性。AP-1结合活性呈双相性,在20分钟内上升4倍,然后恢复到基础水平,然后在2小时内稳步上升至相对于基础值的高水平。这些蛋白激酶c偶联转录因子可能调节内皮基因剪切应力响应和具有适当的结合位点在启动子区域。(C) 1994学术出版社,Inc.
Hemodynamic shear stress forces influence several important endothelial genes associated with arterial relaxation, pro/anti-coagulation, and growth control; however, the regulatory pathways remain unclear. Here we demonstrate stimulation of DNA binding activities of nuclear factor kappa B (NF kappa B), a member of the Rel Family of transcription factors, and nuclear factor activator protein-1 (AP-1) following exposure of endothelial cells to unidirectional shear stress in laminar flow. NF kappa B binding was stimulated within 30 minutes, reaching and maintaining maximal levels at 1 hour. DNA binding activity was inhibited by pre-incubation of nuclear extract with antibody directed against NF kappa B p65 subunit. AP-1 binding activity was biphasic, rising fourfold within 20 minutes and returning to basal levels before steadily increasing by 2 hours to a high level relative to basal values. These protein kinase C-coupled transcriptional factors may modulate endothelial genes that are shear stress-responsive and that possess appropriate binding sites in the promoter region. (C) 1994 Academic Press, Inc.