IMR Press / FBE / Volume 4 / Issue 7 / DOI: 10.2741/E573

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Imidazolineoxyl N-oxide induces COX-2 in endothelial cells: role of free radicals

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1 Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research, II-B Sant Pau, c/ Antoni Ma Claret 167, 08025 Barcelona, Spain
2 Centro de Investigacion Cardiovascular (CSIC-ICCC), Institute of Biomedical Research, II-B Sant Pau, c/ Antoni Ma Claret 167, 08025 Barcelona, Spain
3 Vascular Surgery Department, Institute of Biomedical Research, II-B Sant Pau, c/ Antoni Ma Claret 167, 08025 Barcelona, Spain

*Author to whom correspondence should be addressed.

Academic Editor: Ana Fortuno

Front. Biosci. (Elite Ed) 2012, 4(7), 2654–2669; https://doi.org/10.2741/E573
Published: 1 June 2012
Abstract

cPTIO (2-[4-carboxyphenyl]-4,4,5,5- tetramethylimidazoline-1-oxyl-3-oxide) exerts beneficial actions on systemic inflammatory response. Besides its nitric oxide (NO) scavenging properties cPTIO could exert beneficial effects through modulation of arachidonic acid metabolism. We studied the effect of cPTIO on the biosynthesis of vasoactive prostaglandins (PG) by endothelial cells. Human cord umbilical vein endothelial cells (HUVEC) were treated with cPTIO, and expression of cycloxygenase (COX) isoenzymes in terms of mRNA and protein was determined by real-time-PCR and immunoblotting. Release of PGE2 (as index of untransformed PGH2 release) and 6-oxoPGF1alpha (PGI2 stable metabolite) was determined by enzymeimmunoassay. cPTIO significantly increases the release of untransformed PGH2 associated to the induction of COX-2 expression. Experiments with NO-synthase inhibitors and radical scavengers showed that induction of COX-2 by cPTIO was mediated by free radical species, likely caused by the mobilization of NO from cellular stores. Finally, using specific signaltransduction inhibitors we show the involvement of Src/PI3- K/PKC pathway. Additional effects other than a direct NO scavenging activity may confer therapeutic advantages to cPTIO as compared with NO-synthase inhibitors for the treatment of systemic inflammation-associated vascular hyporeactivity.

Keywords
cPTIO
COX-2
Endothelial cell
Nitric oxide
PI3K
PKC
Src
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