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

David Sacerdoti, Claudia Colombrita, Marco Di Pascoli, Michal L. Schwartzman, Massimo Bolognesi, John R. Falck, Angelo Gatta, Nader G. Abraham

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)155-161
Number of pages7
JournalProstaglandins and Other Lipid Mediators
Volume82
Issue number1-4
DOIs
StatePublished - Jan 1 2007

Keywords

  • 11,12-EET
  • CO
  • Carbon monoxide
  • Endothelial cell
  • Epoxygenase
  • HO-1
  • Heme oxygenase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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