11,12-Epoxyeicosatrienoic acid stimulates heme-oxygenase-1 in endothelial cells

As epoxyeicosatrienoic acids (EETs), particularly 11,12-EET, and the heme oxygenase/carbon monoxide (HO/CO) system share overlapping biological activities, we examined a possible link between 11,12-EET and HO activity in endothelial cells. Confocal microscopy analysis of immunostaining of HO-1 and H...

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Bibliographic Details
Published in:Prostaglandins & other lipid mediators 2007, Vol.82 (1), p.155-161
Main Authors: Sacerdoti, David, Colombrita, Claudia, Di Pascoli, Marco, Schwartzman, Michal L., Bolognesi, Massimo, Falck, John R., Gatta, Angelo, Abraham, Nader G.
Format: Article
Language:English
Subjects:
11,12-EET
8,11,14-Eicosatrienoic Acid - analogs & derivatives
8,11,14-Eicosatrienoic Acid - metabolism
Blotting, Western
Carbon monoxide
Endothelial cell
Endothelial Cells - drug effects
Endothelial Cells - enzymology
Epoxygenase
Gene Expression - drug effects
Heme oxygenase
Heme Oxygenase (Decyclizing) - metabolism
Heme Oxygenase-1 - metabolism
HO-1
Humans
Metalloporphyrins - pharmacology
Microscopy, Confocal
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Summary:As epoxyeicosatrienoic acids (EETs), particularly 11,12-EET, and the heme oxygenase/carbon monoxide (HO/CO) system share overlapping biological activities, we examined a possible link between 11,12-EET and HO activity in endothelial cells. Confocal microscopy analysis of immunostaining of HO-1 and HO-2 in cultured endothelial cells treated with 11,12-EET (1 μM) showed an increase in florescence of HO-1 protein in the various cellular compartments, but not of HO-2. Incubation of endothelial cells with 11,12-EET (1 μM) for 24 h increased the level of HO-1 protein by about three-fold. Similarly, incubation of endothelial cells with 8,9-EET and sodium nitroprussiate, a known inducer of HO-1, increased HO-1 protein without any effect on HO-2. Upregulation of HO-1 by 11,12-EET, as well as 8,9-EET, was associated with an increase in HO activity, which was inhibited by stannous mesoporphirin (10 μM). Incubation of rat aortas with 11,12-EET (1 μM for 60 min) increased HO activity. These findings identify a novel effect of EETs on endothelial HO-1 and indicate that the signaling pathway of EETs in endothelial cells is possibly via an increase in HO-1 expression and activity.
ISSN:1098-8823
DOI:10.1016/j.prostaglandins.2006.07.001