IκBα-dependent regulation of low-shear flow-induced NF-κB activity:: role of nitric oxide

被引:36
作者
Mohan, S
Hamuro, M
Sorescu, GP
Koyoma, K
Sprague, EA
Jo, HJ
Valente, AJ
Prihoda, TJ
Natarajan, M
机构
[1] Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA
[2] Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA
[3] Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA
[4] Univ Texas, Hlth Sci Ctr, Dept Radiat Oncol, San Antonio, TX 78229 USA
[5] Georgia Tech Res Inst, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30322 USA
[6] Emory Univ, Atlanta, GA 30322 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2003年 / 284卷 / 04期
关键词
low shear stress; inhibitor kappa B; endothelial nitric oxide synthase; nuclear factor-kappa B;
D O I
10.1152/ajpcell.00464.2001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have investigated the role of inhibitor kappaBalpha (IkappaBalpha) in the activation of nuclear factor kappaB (NF-kappaB) observed in human aortic endothelial cells (HAEC) undergoing a low shear stress of 2 dynes/cm(2). Low shear for 6 h resulted in a reduction of IkappaBalpha levels, an activation of NF-kappaB, and an increase in kappaB-dependent vascular cell adhesion molecule 1 (VCAM-1) mRNA expression and endothelial-monocyte adhesion. Overexpression of IkappaBalpha in HAEC attenuated all of these shear-induced responses. These results suggest that downregulation of IkappaBalpha is the major factor in the low shear-induced activation of NF-kappaB in HAEC. We then investigated the role of nitric oxide (NO) in the regulation of IkappaBalpha/NF-kappaB. Overexpression of endothelial nitric oxide synthase (eNOS) inhibited NF-kappaB activation in HAEC exposed to 6 h of low shear stress. Addition of the structurally unrelated NO donors S-nitrosoglutathione (300 muM) or sodium nitroprusside (1 mM) before low shear stress significantly increased cytoplasmic IkappaBalpha and concomitantly reduced NF-kappaB binding activity and kappaB-dependent VCAM-1 promoter activity. Together, these data suggest that NO may play a major role in the regulation of IkappaBalpha levels in HAEC and that the application of low shear flow increases NF-kappaB activity by attenuating NO generation and thus IkappaBalpha levels.
引用
收藏
页码:C1039 / C1047
页数:9
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