Original ContributionsThe protective role of plasmalogens in iron-induced lipid peroxidation☆
Introduction
Plasmalogens are a special group of phospholipids characterized by a vinyl ether bond instead of an ester bond in the sn-1 position. In mammals, this form of phospholipid is restricted to phosphatidyl-ethanolamine (PE) and -choline (PC), and constitutes a few percent of the total phospholipid in most tissues and cells [1]. However, in nervous tissue, heart muscle, testis, kidney and certain blood cells, the concentration of plasmalogens is considerable and constitutes 15–85% of the total PE and PC. The vinyl ether-linked aliphatic moieties in the sn-1 position consist almost exclusively of palmitic (16:0), stearic (18:0) and oleic (18:1) carbon chains and form corresponding fatty aldehydes upon acid hydrolysis. As in most other phospholipids, the sn-2 position is mainly occupied by polyunsaturated fatty acids (PUFA). In contrast to the ester phospholipids, the initial two enzymes of plasmalogen biosynthesis are localized in peroxisomes and consequently, the synthesis of ether lipids is separately regulated from that of other phospholipids [2].
The biological function of plasmalogens is unclear but it has been proposed that they may play a role in antioxidant defense. Plasmalogens can protect cells against photosensitized killing (i.e., against singlet oxygen toxicity [3], [4]). On the other hand, heating a long chain vinyl ether in the presence of PUFA esters resulted in an increased breakdown of the former, indicating that the vinyl ether function of plasmalogens is prone to autoxidation [5]. Recently, it has also been suggested that plasmalogens can protect against iron- and copper-dependent lipid peroxidation [6], [7]. In one of these studies, it was proposed that the antioxidant effect was due to chelation of transition metal ions [7].
In this study, we have investigated the role of plasmalogens in lipid peroxidation by using various liposomal systems and different peroxidation inducers. By comparing the various systems, we were able to exclude all variables apart from the vinyl ether function, and show that plasmalogens strongly influence the lipid peroxidative process.
Section snippets
Materials and methods
Human brain from autopsy samples and rat liver were used for preparation of phospholipids. Tissue homogenates (20%, w/v) were prepared in 0.15 M KCl with an Ultra-Turrax blender and extracted with chloroform/methanol/water (1:1:0.3, v/v) for 60 min at 40°C with magnetic stirring [8]. The mixture was centrifuged (1200 g, 15 min) and the supernatant transferred to a new tube. The pelleted residue was re-extracted with 5 ml of chloroform/methanol (2:1, v/v), after which 1 ml of methanol was added
Results
Two liposomal systems were employed for the study of plasmalogen effects on lipid peroxidation. In the first system, total brain phospholipids were compared to total brain phospholipids after acid hydrolysis of plasmalogens and removal of aldehydes. Thus, these two phospholipid populations had an identical fatty acid composition and differed only in plasmalogen and lyso-PE content. The second system consisted of PC/PE (3:1) liposomes where PE was either diacyl-PE or alkenylacyl-PE, which
Discussion
The purpose of this study was to evaluate the involvement of plasmalogens in lipid peroxidation. Several tissues, such as brain and heart, have a high content of plasmalogens while other tissues contain negligible amounts. Since free radicals have been implicated in the pathogenesis of Alzheimer’s disease [19], Parkinson’s disease [20], reperfusion syndrome [21] and atherosclerosis [22], it is of considerable interest to define various factors that can influence or modify peroxidative stress in
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This work was supported by the Swedish Cancer Society and the Swedish Medical Research Council.