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

Prostaglandins Other Lipid Mediat. 2007 Jan;82(1-4):155-61. doi: 10.1016/j.prostaglandins.2006.07.001. Epub 2006 Aug 30.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8,11,14-Eicosatrienoic Acid / analogs & derivatives*
  • 8,11,14-Eicosatrienoic Acid / metabolism
  • Blotting, Western
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology*
  • Gene Expression / drug effects
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Metalloporphyrins / pharmacology
  • Microscopy, Confocal

Substances

  • Metalloporphyrins
  • stannous mesoporphyrin
  • 11,12-epoxy-5,8,14-eicosatrienoic acid
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • heme oxygenase-2
  • 8,11,14-Eicosatrienoic Acid