Copper-induced lipid peroxidation in liposomes, micelles, and LDL: Which is the role of vitamin E?

Abstract

Liposomes, containing phospholipid hydroperoxides, are peroxidised in the presence of Cu ++. Peroxidation starts after a period of resistance to oxidation, which is abolished by the shift of lipid organisation from bilayer to micellar dispersion. Independently from ongoing peroxidation, vitamin E in liposomes also reacts with Cu ++, and it is consumed. The evidence that phospholipid hydroperoxides induce an acceleration of vitamin E consumption rate and that the consumption of vitamin E and phospholipid hydroperoxides are stoichiometric indicates that, in liposomes, the rate-limiting reaction is the interaction between radicals generated by copper from vitamin E and phospholipid hydroperoxides. In micelles, on the other hand, vitamin E is directly oxidised by copper at a much faster rate; thus, the concerted consumption of phospholipid hydroperoxides does not take place. Moreover, in micelles challenged with Cu ++, vitamin E plays a pro-oxidant effect (M. Maiorino et al. FEBS Letts., 330(2):174–176; 1993). In LDL, incubation with Cu ++ promotes vitamin E consumption at a fast rate, as in micelles, but not the concerted disappearance of lipid hydroperoxides, as in liposomes. However, the direct vitamin E oxidation by Cu ++, observed in micelles and liposomes, does not lead to a pro-oxidant effect in LDL. The kinetics of peroxidation, indeed, is identical in native and vitamin E-depleted LDL. These results argue against an involvement of vitamin E, both as antioxidant or pro-oxidant in LDL challenged with Cu ++, and suggest that other factors, besides antioxidant content, must be relevant in determining LDL oxidative resistance.