IkappaBalpha-dependent regulation of low-shear flow-induced NF-kappa B activity: role of nitric oxide |
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Authors: | Mohan Sumathy Hamuro Masao Sorescu George P Koyoma Koichi Sprague Eugene A Jo Hanjoong Valente Anthony J Prihoda Thomas J Natarajan Mohan |
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Institution: | Department of Pathology, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA. mohan@uthscsa.edu |
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Abstract: | We have investigated the role ofinhibitor B (I B ) in the activation of nuclear factor B(NF- B) observed in human aortic endothelial cells (HAEC) undergoinga low shear stress of 2 dynes/cm2. Low shear for 6 hresulted in a reduction of I B levels, an activation of NF- B,and an increase in B-dependent vascular cell adhesion molecule 1 (VCAM-1) mRNA expression and endothelial-monocyte adhesion.Overexpression of I B in HAEC attenuated all of these shear-induced responses. These results suggest that downregulation ofI B is the major factor in the low shear-induced activation ofNF- B in HAEC. We then investigated the role of nitric oxide (NO) inthe regulation of I B /NF- B. Overexpression of endothelial nitric oxide synthase (eNOS) inhibited NF- B activation in HAEC exposed to 6 h of low shear stress. Addition of the structurally unrelated NO donors S-nitrosoglutathione (300 µM) orsodium nitroprusside (1 mM) before low shear stress significantlyincreased cytoplasmic I B and concomitantly reduced NF- Bbinding activity and B-dependent VCAM-1 promoter activity. Together,these data suggest that NO may play a major role in the regulation ofI B levels in HAEC and that the application of low shear flowincreases NF- B activity by attenuating NO generation and thusI B levels. |
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