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11,12-epoxyeicosatrienoic acid stimulates heme-oxygenase-1 in endothelial cells
Authors:Sacerdoti David  Colombrita Claudia  Di Pascoli Marco  Schwartzman Michal L  Bolognesi Massimo  Falck John R  Gatta Angelo  Abraham Nader G
Affiliation:Department of Clinical and Experimental Medicine, Clinica Medica 5, University of Padova, Via Giustiniani 2, 35100 Padova, Italy. david.sacerdoti@unipd.it
Abstract: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 microM) 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 microM) 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 microM). Incubation of rat aortas with 11,12-EET (1 microM 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.
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