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

Sumathy Mohan, Masao Hamuro, George P. Sorescu, Koichi Koyoma, Eugene A. Sprague, Hanjoong Jo, Anthony J. Valente, Thomas J. Prihoda, Mohan Natarajan

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

We have investigated the role of inhibitor κBα (IκBα) in the activation of nuclear factor κB (NF-κB) observed in human aortic endothelial cells (HAEC) undergoing a low shear stress of 2 dynes/cm2. Low shear for 6 h resulted in a reduction of IκBα levels, an activation of NF-κB, and an increase in κB-dependent vascular cell adhesion molecule 1 (VCAM-1) mRNA expression and endothelial-monocyte adhesion. Overexpression of IκBα in HAEC attenuated all of these shear-induced responses. These results suggest that downregulation of IκBα is the major factor in the low shear-induced activation of NF-κB in HAEC. We then investigated the role of nitric oxide (NO) in the regulation of IκBα/NF-κB. Overexpression of endothelial nitric oxide synthase (eNOS) inhibited NF-κB activation in HAEC exposed to 6 h of low shear stress. Addition of the structurally unrelated NO donors S-nitrosoglutathione (300 μM) or sodium nitroprusside (1 mM) before low shear stress significantly increased cytoplasmic IκBα and concomitantly reduced NF-κB binding activity and κB-dependent VCAM-1 promoter activity. Together, these data suggest that NO may play a major role in the regulation of IκBα levels in HAEC and that the application of low shear flow increases NF-κB activity by attenuating NO generation and thus IκBα levels.

Original languageEnglish (US)
Pages (from-to)C1039-C1047
JournalAmerican Journal of Physiology - Cell Physiology
Volume284
Issue number4 53-4
DOIs
StatePublished - Apr 1 2003

Keywords

  • Endothelial nitric oxide synthase
  • Inhibitor κB
  • Low shear stress
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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