Novel physiological function of sphingomyelin in plasma - Inhibition of lipid peroxidation in low density lipoproteins

Although sphingomyelin (SPH) is a major constituent of all lipoproteins, it s physiological function in plasma is not known. In this study, we tested t he hypothesis that SPH inhibits lipid peroxidation in low density lipoprote ins (LDL) because of its effects on surface fluidity and packing density an d that the relative resistance of the buoyant LDL to oxidation, compared wi th the dense LDL, is partly due to their higher SPH content, Depletion of S PH by treatment with SPHase resulted in shortened lag times and increased r ates of oxidation in both LDL subfractions, as measured by the conjugated d iene formation in the presence of Cu2+, Oxidation of LDL by soybean lipoxyg enase was similarly stimulated by the degradation of SPH, Oxidation-induced fluorescence decay of diphenylhexatriene-labeled phosphatidylcholine (PC), equilibrated with LDL-PC, was accelerated significantly by the enzymatic d epletion of SPH from the lipoprotein, Oxidation of 16:0-18:2 PC in the prot eoliposomes was inhibited progressively by the incorporation of increasing amounts of egg SPH into the Liposomes, Treatment of SPH-containing proteoli posomes with SPHase reversed the effect of SPH, showing that the presence o f intact SPH is necessary for the inhibition of oxidation, Although the inc orporation of SPH into the same liposome as the PC (intrinsic SPH) protecte d the PC against oxidation, the addition of SPH liposomes to PC liposomes ( extrinsic SPH) was not effective. Oxidation of 16:0-18:2 PC in liposomes wa s also inhibited by the incorporation of dipalmitoyl-PC, but not by fi ee c holesterol, These results suggest that SPH acts as a physiological inhibito r of lipoprotein oxidation, possibly by modifying the fluidity of the phosp holipid monolayer and thereby inhibiting the lateral propagation of the lip id peroxy radicals.