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 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume284
Issue number4 53-4
StatePublished - Apr 1 2003

Fingerprint

Endothelial cells
Shear flow
Nitric Oxide
Endothelial Cells
Chemical activation
Shear stress
Vascular Cell Adhesion Molecule-1
S-Nitrosoglutathione
Nitric Oxide Donors
Nitric Oxide Synthase Type III
Nitroprusside
Monocytes
Down-Regulation
Adhesion
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Mohan, S., Hamuro, M., Sorescu, G. P., Koyoma, K., Sprague, E. A., Jo, H., ... Natarajan, M. (2003). IκBα-dependent regulation of low-shear flow-induced NF-κB activity: Role of nitric oxide. American Journal of Physiology - Cell Physiology, 284(4 53-4).

IκBα-dependent regulation of low-shear flow-induced NF-κB activity : Role of nitric oxide. / Mohan, Sumathy; Hamuro, Masao; Sorescu, George P.; Koyoma, Koichi; Sprague, Eugene A; Jo, Hanjoong; Valente, Anthony J.; Prihoda, Thomas J.; Natarajan, Mohan.

In: American Journal of Physiology - Cell Physiology, Vol. 284, No. 4 53-4, 01.04.2003.

Research output: Contribution to journalArticle

Mohan, S, Hamuro, M, Sorescu, GP, Koyoma, K, Sprague, EA, Jo, H, Valente, AJ, Prihoda, TJ & Natarajan, M 2003, 'IκBα-dependent regulation of low-shear flow-induced NF-κB activity: Role of nitric oxide', American Journal of Physiology - Cell Physiology, vol. 284, no. 4 53-4.
Mohan, Sumathy ; Hamuro, Masao ; Sorescu, George P. ; Koyoma, Koichi ; Sprague, Eugene A ; Jo, Hanjoong ; Valente, Anthony J. ; Prihoda, Thomas J. ; Natarajan, Mohan. / IκBα-dependent regulation of low-shear flow-induced NF-κB activity : Role of nitric oxide. In: American Journal of Physiology - Cell Physiology. 2003 ; Vol. 284, No. 4 53-4.
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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.",
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