Abstract
Free radical driven lipid peroxidation is a chain reaction which can lead to oxidative degradation of biological membranes. Propagation vs. termination rates of peroxidation in biological membranes are determined by a variety of factors including fatty acyl chain composition, presence of antioxidants, as well as biophysical properties of mono- or bilayers. Sphingomyelins (SMs), a class of sphingophospholipids, were previously described to inhibit lipid oxidation most probably via the formation of H-bond network within membranes. To address the “antioxidant” potential of SMs, we performed LC-MS/MS analysis of model SM/glycerophosphatidylcholine (PC) liposomes with different SM fraction after induction of radical driven lipid peroxidation. Increasing SM fraction led to a strong suppression of lipid peroxidation. Electrochemical oxidation of non-liposomal SMs eliminated the observed effect, indicating the importance of membrane structure for inhibition of peroxidation propagation. High resolution MS analysis of lipid peroxidation products (LPPs) observed in in vitro oxidized SM/PC liposomes allowed to identify and relatively quantify SM- and PC-derived LPPs. Moreover, mapping quantified LPPs to the known pathways of lipid peroxidation allowed to demonstrate significant decrease in mono-hydroxy(epoxy) LPPs relative to mono-keto derivatives in SM-rich liposomes. The results presented here illustrate an important property of SMs in biological membranes, acting as “biophysical antioxidant”. Furthermore, a ratio between mono-keto/mono-hydroxy(epoxy) oxidized species can be used as a marker of lipid peroxidation propagation in the presence of different antioxidants.
Highlights
Lipid peroxidation is a degradation process commonly initiated by reactive oxygen species (ROS) [1]and correlated to several pathologies, such as atherosclerosis [2], neurodegenerative diseases [3], type 2 diabetes [4], chronic inflammation [5], and age-associated diseases [6]
The overall rate of lipid oxidation in biological membranes is determined by a complex set of factors including the composition of polyunsaturated fatty acyl chains of PLs, presence and ratio of radical trapping antioxidants (e.g., α-tocopherol and CoQ10), and membrane biophysical properties, such as fluidity and rigidity [13,14,15,16,17]
Using electrochemical oxidation, we demonstrated that this is effect is eliminated in non-liposomal SM solutions, underlying the importance of membrane organization and H-bond network
Summary
Lipid peroxidation is a degradation process commonly initiated by reactive oxygen species (ROS) [1]. High SM content, and ability to form dense H-bond network between SMs and SM and cholesterol, lead to phase segregation with the formation of a liquid ordered phase [Lo] in lipid rafts, in contrast to a liquid disordered phase [Ld] in the main membrane domain. Using liposomes of different lipid compositions, it was demonstrated that higher SM content correlates with lower amount of formed conjugated dienes, markers of oxidized PUFA chains [26]. The possibility of formation of biologically relevant SM-derived lipid peroxidation products (LPPs) cannot be excluded, since, even if in lower abundance, SMs composed by unsaturated fatty acids (FA) are known to be present in biological systems. A detailed molecular characterization of formed LPPs allowed us to demonstrate the redirection of lipid peroxidation pathway from chain propagation, yielding lipid hydroxides/epoxides, towards chain termination, with the formation of corresponding keto derivatives, in the presence of increasing amounts of SMs
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