Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-13381
Stähli, B E; Breitenstein, A; Akhmedov, A; Camici, G G; Shojaati, K; Bogdanov, N; Steffel, J; Ringli, D; Lüscher, T F; Tanner, F C (2007). Cardiac glycosides regulate endothelial tissue factor expression in culture. Arteriosclerosis, Thrombosis, and Vascular Biology, 27(12):2769-2776.
BACKGROUND: Tissue factor (TF) plays an important role in acute coronary syndromes and stent thrombosis. This study investigates whether Na(+)/K(+)-ATPase regulates TF expression in human endothelial cells. METHODS AND RESULTS: Ouabain inhibited tumor necrosis factor (TNF)-alpha-induced endothelial TF protein expression; maximal inhibition occurred at 10(-5) mol/L, reached more than 70%, and was observed throughout the 5 hours stimulation period. The decrease in protein expression was paralleled by a reduced TF surface activity. Similarly, lowering of extracellular potassium concentration inhibited TNF-alpha-induced TF protein expression. In contrast, ouabain did not affect TNF-alpha-induced expression of full-length TF mRNA for up to 5 hours of stimulation; instead, expression of alternatively-spliced TF mRNA was upregulated after 3 and 5 hours of stimulation. Ouabain did not affect TNF-alpha-induced activation of the MAP kinases p38, extracellular signal-regulated kinase (ERK), and c-Jun terminal NH(2) kinase; activation of Akt and p70S6 kinase remained unaltered as well. Similar to the MAP kinases, ouabain did not affect TNF-alpha-induced degradation of IkappaB-alpha. Ouabain had no effect on TF protein degradation. CONCLUSIONS: Na(+)/K(+)-ATPase is required for protein translation of endothelial TF in culture. This observation provides novel insights into posttranscriptional regulation of TF expression.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||05 Vetsuisse Faculty > Institute of Veterinary Physiology|
04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||19 Mar 2009 18:47|
|Last Modified:||23 Nov 2012 14:06|
|Publisher:||Lippincott Wiliams & Wilkins|
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