Differential effects of long chain n-3 fatty acids on the expression of PGH synthase isoforms in bovine aortic endothelial cells.

Primary cultures of bovine aortic endothelial cells were used at confluency to evaluate the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on the expression of both the constitutive and inducible isoforms of PGH synthase (PGHS), PGHS-1 and PGHS-2, respectively. After a 22 h period enrichment of cell lipid stores with each fatty acid, the expression of PGH synthase isoforms was measured by western blotting. EPA and DHA, but not oleate, significantly decreased the immunoreactive PGHS-1 and to a similar extent the corresponding mRNA, as measured by northern blotting. Studies on mRNA stability failed to show any difference between DHA-enriched and control cells, indicating that the decreased expression observed was likely from transcriptional origin. Under the enrichment conditions, EPA and DHA, but not oleate, moderately but significantly induced an oxidative stress as judged by malondialdehyde formation. Interestingly, hydrogen peroxide was able to mimic the effect of EPA and DHA in decreasing the expression of PGHS-1. On the other hand, the PMA-induced PGHS-2 expression could be potentiated by cell pre-enrichment with DHA, whereas hydrogen peroxide alone could induce such an expression. We conclude that the long chain n-3 fatty acids EPA and DHA may differently affect the expression of PGH synthase isoforms, possibly via an oxidative stress.