Dual regulation of glutathione peroxidase by docosahexaenoic acid in endothelial cells depending on concentration and vascular bed origin

Docosahexaenoic acid (DHA) has been reported to elicit oxidative stress, wh ich in turn can induce antioxidant enzymes. Glutathione peroxidase (GPx) ha s received particular attention in this respect, as this enzyme is specific ally required for the degradation of lipid hydroperoxides. Because we previ ously found that DHA could protect against oxidative stress when used in lo w amounts, we have compared the effect of a low (10 muM) versus high (100 m uM) concentration of DHA on oxidant/antioxidant balance in bovine retinal a nd bovine aortic endothelial cells (BREC and BAEC). At 100 muM, DHA elicite d a marked oxidative stress, as evidenced by high malondialdehyde levels an d decreased plasmalogen phosphatidylethanolamine in both cells, and for BAE C only, a decrease of cu-tocopherol. At 10 muM, DHA induced a slight increa se of malondialdehyde in both cells, but did not affect cu-tocopherol level s, which is indicative of a mild oxidative stress. In BREC, 10 muM DHA slig htly but significantly decreased cytosolic GPx (cGPx) activity whereas 100 muM had no effect. In contrast, in BAEC, DHA 10 muM did not affect cGPx act ivity, whereas 100 muM increased it. The decreased cGPx activity in BREC wa s associated with a lower level of protein, suggesting a transcriptional an d/or posttranscriptional effect. Phospholipid hydroperoxide GPx (PHGPx) act ivity was not modified by DHA at either concentration in BREC, whereas it w as increased in BAEC when using 100 muM. Our results confirm that large amo unts of DHA lead to oxidative stress, but do no support an antioxidant acti on of DHA at low concentration, in endothelium. Nevertheless, we showed tha t DHA can exert opposite effects on GPx regulation in endothelial cells, wi th regard to its concentration and to vascular bed origin. (C) 2001 Elsevie r Science Inc.