title: Novel physiological function of sphingomyelin in plasma. Inhibition of lipid peroxidation in low density lipoproteins.
abstract: Although sphingomyelin (SPH) is a major constituent of all lipoproteins, its physiological function in plasma is not known. In this study, we tested the hypothesis that SPH inhibits lipid peroxidation in low density lipoproteins (LDL) because of its effects on surface fluidity and packing density and that the relative resistance of the buoyant LDL to oxidation, compared with the dense LDL, is partly due to their higher SPH content. Depletion of SPH by treatment with SPHase resulted in shortened lag times and increased rates of oxidation in both LDL subfractions, as measured by the conjugated diene formation in the presence of Cu(2+). Oxidation of LDL by soybean lipoxygenase 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 depletion of SPH from the lipoprotein. Oxidation of 16:0-18:2 PC in the proteoliposomes was inhibited progressively by the incorporation of increasing amounts of egg SPH into the liposomes. Treatment of SPH-containing proteoliposomes with SPHase reversed the effect of SPH, showing that the presence of intact SPH is necessary for the inhibition of oxidation. Although the incorporation of SPH into the same liposome as the PC (intrinsic SPH) protected 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 was also inhibited by the incorporation of dipalmitoyl-PC, but not by free cholesterol. These results suggest that SPH acts as a physiological inhibitor of lipoprotein oxidation, possibly by modifying the fluidity of the phospholipid monolayer and thereby inhibiting the lateral propagation of the lipid peroxy radicals.
authors.affiliation: Departments of Medicine and Biochemistry, Rush Medical College, Chicago, Illinois 60612, USA. psubbaia@rush.edu
authors.forename: P V
authors.initials: PV
authors.lastname: Subbaiah
authors.forename: V S
authors.initials: VS
authors.lastname: Subramanian
authors.forename: K
authors.initials: K
authors.lastname: Wang
mesh_terms: D004337:Drug Carriers; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood*; D008081:Liposomes; D013109:Sphingomyelins / Q000097:blood* / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D008077:Lipoproteins, LDL; D008081:Liposomes; D013109:Sphingomyelins