DIFFERENTIAL-EFFECTS OF ENDOTHELIAL-CELL FATTY-ACID MODIFICATION ON THE SENSITIVITY OF THEIR MEMBRANE PHOSPHOLIPIDS TO PEROXIDATION

In order to study the relationship between the fatty acid (FA) composi tion of human umbilical vein endothelial cells (HUVEC) and their susce ptibility to oxidative stress, we modified their FA composition by lon g-term culturing in media supplemented,vith a saturated, monounsaturat ed, or polyunsaturated FA, Sensitivity of the cellular phospholipids t o peroxidation was monitored by measuring conjugated diene formation a nd decrease of polyunsaturated FAs induced by CuSO4 and H2O2 in liposo mes prepared from the respective phospholipid extracts, The extent of phospholipid peroxidation was found to increase with increasing conten t of polyunsaturated FAs. In addition, the sensitivity of individual p olyunsaturated FAs to peroxidation was directly proportional to the nu mber of double bonds present, However, no unequivocal relationship was observed between conjugated diene formation and the phospholipid unsa turation index (an indicator for the combined effect of number of doub le bonds and polyunsaturated FA contents of the membrane phospholipids ). The results suggest that long-term FA modification of endothelial c ells differentially alters the sensitivity of their membrane phospholi pids to peroxidation: long-term modification with oleic acid may prote ct against lipid peroxidation, whereas linoleic acid may increase sens itivity to peroxidation. In contrast to what might be expected, long-t erm modification of endothelial cells with eicosapentaenoic or docosah exaenoic acid does not increase the sensitivity of phospholipids to pe roxidation.