EFFECTS OF FATTY-ACIDS ON HUMAN PLATELET GLUTATHIONE-PEROXIDASE - POSSIBLE ROLE OF OXIDATIVE STRESS

Highly polyunsaturated fatty acids of the n-3 family are known to be i nhibitors of platelet functions, but these fatty acids (FA) may alter the platelet antioxidant status, depending on their concentrations. Th e present study was aimed to investigate the effect of various FA on g lutathione-dependent peroxidase (GPx), the required antioxidant enzyme for degrading FA hydroperoxides. Human platelets were enriched in vit ro with either n-3 (18:3, 20:5, or 22:6), n-6 (18:2 or 18:3) FA, 18:1n -9 or 16:0, and the GPx activity was then measured. It was found that n-3 FA enhanced the GPx activity whereas the others did not affect the enzyme activity. The increased GPx activity was associated with an in creased amount of the enzyme measured by Western blotting. The enhance d activity and amount of GPx induced by 22:6n-3, the most potent activ ator among the n-3 FA, was completely abolished in the presence of cyc loheximide at a concentration known to inhibit platelet protein synthe sis. Because platelets are devoid of nucleus, which rules out the invo lvement of transcriptional factors, this suggests that 22:6n-3 might a ct at a translational level. On the other hand, 22:6n-3 treatment incr eased the malondialdehyde formation and decreased the vitamin E level in platelets, both events that could be prevented by the antioxidant e picatechin. Because epicatechin also suppressed the enhancement of bot h the activity and amount of GPx induced by 22:6n-3, we conclude that the increased GPx activity (possibly via protein synthesis) might be a ssociated with an oxidative stress induced by 22:6n-3 and/or 20:4n-6 r eleased from the platelet endogenous pool in the course of the 22:6n-3 enrichment. (C) 1997 Elsevier Science Inc.