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 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.
Sacerdoti
David
D
Department of Clinical and Experimental Medicine, Clinica Medica 5, University of Padova, Via Giustiniani 2, 35100 Padova, Italy. david.sacerdoti@unipd.it
Colombrita
Claudia
C
Di Pascoli
Marco
M
Schwartzman
Michal L
ML
Bolognesi
Massimo
M
Falck
John R
JR
Gatta
Angelo
A
Abraham
Nader G
NG
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015153:Blotting, Western; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D015870:Gene Expression / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D008665:Metalloporphyrins / Q000494:pharmacology; D018613:Microscopy, Confocal
D008665:Metalloporphyrins; C518404:stannous mesoporphyrin; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D015126:8,11,14-Eicosatrienoic Acid