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 inhibitors of platelet functions, but these fatty acids (FA) may alter the platelet antioxidant status, depending on their concentrations. The present study was aimed to investigate the effect of various FA on glutathione-dependent peroxidase (GPx), the required antioxidant enzyme for degrading FA hydroperoxides. Human platelets were enriched in vitro with either n-3 (18:3, 20.5, or 22.6), n-6 (18:2 or 18:3) FA, 18:1 n-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 increased amount of the enzyme measured by Western blotting. The enhanced activity and amount of GPx induced by 22:6n-3, the most potent activator among the n-3 FA, was completely abolished in the presence of cycloheximide at a concentration known to inhibit platelet protein synthesis. Because platelets are devoid of nucleus, which rules out the involvement of transcriptional factors, this suggests that 22:6n-3 might act at a translational level. On the other hand, 22:6n-3 treatment increased the malondialdehyde formation and decreased the vitamin E level in platelets, both events that could be prevented by the antioxidant epicatechin. Because epicatechin also suppressed the enhancement of both the activity and amount of GPx induced by 22:6n-3, we conclude that the increased GPx activity (possibly via protein synthesis) might be associated with an oxidative stress induced by 22:6n-3 and/or 20:4n-6 released from the platelet endogenous pool in the course of the 22:6n-3 enrichment.
Lemaitre
D
D
INSERM U352, Biochimie et Pharmacologie, INSA-LYON, Villeurbanne, France.
Véricel
E
E
Polette
A
A
Lagarde
M
M
D001792:Blood Platelets / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D014810:Vitamin E / Q000032:analysis
D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D014810:Vitamin E; D005979:Glutathione Peroxidase