Thorolf Brosche

THE BIOLOGICAL SIGNIFICANCE OF PLASMALOGENS IN DEFENSE AGAINST OXIDATIVE DAMAGE

The phospholipid class of plasmalogens is ubiquitously found in considerable amounts as a constituent of mammalian cell membranes and of plasma lipoproteins. Plasmalogens are more susceptible to oxidative reactions compared to their fatty acid ester analogues, due to the reactivity of their enolether function. Studies on plasmalogen-deficient cell lines lead to the proposal that these ether lipids serve as endogenous antioxidants. No clear conclusions regarding the antioxidative effects of plasmalogens could be drawn from studies in patients of different ages with peroxisomal deficiency disorders. A defective peroxisomal plasmalogen synthesis is not necessarily associated with other defects in the metabolism of peroxisomes, as has been established in a cell line recently. In different mammalian tissues a decrease of plasmalogens with age was described. Moreover, an accumulation of plasmalogen oxidation products was measured in brain of old cattle compared to young ones. In pathologic conditions associated with oxidative stress like in spinal cord ischemia and reperfusion, plasmalogen levels varied inversely according to the oxidative burden. Oxidation products of plasmalogens increased with time of ischemia in infarcted porcine heart tissue. Enrichment of lipoproteins with plasmalogens increased their oxidative resistance, which was diminished in the case of LDL particles in patients with coronary arteriosclerosis. In red cell membranes plasmalogens were reduced with donor age and in hyperlipidemia. Under lipid lowering therapy with lovastatin an increase was observed, indicating a possible antioxidative impact of this treatment. Taken together, there is good evidence that plasmalogens are effective as endogenous antioxidants. However, more experimental approaches not confounded by other lipolytic processes are needed to establish this role of plasmalogens.

Effect of borage oil consumption on fatty acid metabolism, transepidermal water loss and skin parameters in elderly people

Human skin is not able to biosynthesize gamma-linolenic acid (GLA, 18:3omega6) from the precursor linoleic acid (LA), or arachidonic acid (AA) from dihomo-gamma-linolenic acid (DHGLA). Dietary supplementation with GLA-rich seed oil of borage skips the step of hepatic 6-desaturation of fatty acids (FA) and, therefore, compensates the lack of these essential FA in conditions with impaired activity of delta 6-desaturase. Twenty-nine healthy elderly people (mean age 68.6 years), received a daily dose of 360 or 720 mg GLA for 2 months, using Borage oil in gelatine capsules (Quintesal 180, manufacturer Galderma Laboratorium GmbH, Freiburg, Germany). The effects of fatty acids derived from ingested borage oil capsules on skin barrier function were assessed by measurement of transepidermal water loss (TEWL). The consumption of borage oil induced a statistically significant improvement of cutaneous barrier function in the elderly people, as reflected in a mean decrease of 10.8% in the transepidermal water loss. Thirty-four percent of the people noted itch before borage oil consumption and 0% afterwards. Dry skin was claimed to be reduced from 42 to 14%, but no significant alteration of skin hydration was measured. The FA-composition of erythrocyte membrane phospholipids demonstrated an increase of GLA (+70%) and DHGLA (+18%) and a reduction of saturated and monounsaturated FA. There was no significant alteration in nervonic acid or in AA content, but an increase in the DHGLA/AA ratio (+23%). Thus, the consumption of borage oil by elderly people lead to alteration of FA metabolism and improved skin function.

Pheromone-XLII. 1,3,6,9-nonadecatetraen, das sexualpheromon des frostspanners operophtera brumata (geometridae).

Abstract By means of GC and GCMS analysis and electrophysiological investigations ( z 3, z 6, z 9)-1,3,6,9-nonadecatetrane was identified as sex pheromone of the winter moth O . brumata , and prepared by stereoselective synthesis methods.

Plasmalogen phospholipids in plasma lipoproteins of normolipidemic donors and patients with hypercholesterolemia treated by LDL apheresis

Recent evidence indicates that plasmalogen phospholipids are particularly sensitive to oxidation and may possess antioxidative properties. Approximately 4.4%-5.5% of phosphatidylcholine (PC), and 53%-60% of phosphatidylethanolamine (PE) consisted of the plasmalogen phospholipids, plasmenylcholine and plasmenylethanolamine, respectively, in whole plasma, low density lipoprotein (LDL) and high density lipoprotein (HDL) of 11 normolipidemic donors. Of total plasmalogen phospholipids in plasma, slightly more was associated with LDL particles (about 42%) than with HDL (36%). Plasmalogen phospholipid levels were analyzed in 12 patients with familial hypercholesterolemia (FH) regularly treated by LDL apheresis, of whom 6 were supplemented with vitamin E (alpha tocopherol, 400 IU/day), the remaining 6 not receiving the antioxidant. Before apheresis (pre), total plasmalogen phospholipid levels in plasma and LDL (expressed as mumol/mmol cholesterol of compartment) decreased as follows: patients receiving vitamin E > normolipidemia > patients not receiving vitamin E. In both hypercholesterolemic groups, the contents of plasmalogen phospholipids in whole plasma and LDL were 3-5-fold higher than those of vitamin E. Directly after apheresis (post), plasmalogen phospholipid levels in plasma were raised by about 50% in the two hypercholesterolemic groups, mostly due to increases in plasmenylethanolamine levels. Two days after apheresis (48 h post), plasmalogen contents were still elevated in plasma and red blood cell membranes of patients receiving vitamin E, while they had already reached pre-apheresis values in those not supplemented with alpha tocopherol. Molecular species of plasma diacyl phospholipids containing polyunsaturated fatty acids were elevated at pre in patients receiving vitamin E as compared to patients without supplementation. At 48 h post, LDL apheresis induced an increase in these molecular species only in patients receiving vitamin E. In conclusion, the contents of plasmalogen phospholipids in plasma lipoproteins are at least three times higher than those of vitamin E. LDL apheresis raises the level of plasmalogen phospholipids in plasma, the increase persisting longer in patients supplemented with vitamin E. Supplementation with vitamin E appears to protect plasmalogen phospholipids in plasma lipoproteins against oxidative degradation.

Plasmalogen phospholipids - facts and theses to their antioxidative qualities.

Fatty aldehyde dimethyl acetals (DMA) derived from plasma and erythrocyte membrane plasmalogen phospholipids of 109 donors, aged 25-91 years, were measured as weight percent of total phospholipid fatty acids and DMA. The age range from 70 to 90 years (n = 82) was divided into age groups of five years each. Cumulative distributions of the DMA values of these age groups, when compared with those of 17 younger persons (aged 25-41 years), revealed a tendency to higher DMA values in the youngest age group, and to lower values in the oldest one. Linear regressions were computed between age and hexadecanaldimethylacetal (16:0 DMA) or octadecanaldimethylactal (18:0 DMA) of erythrocyte membrane and plasma phospholipids. Statistically significant negative correlations with age were obtained. Because of their sensitivity to oxidation reactions, a role of plasmalogens as a natural antioxidant in oxidative defense mechanisms appears to be convincing. However, it will possibly be difficult to separate the effects of normal aging on the decline of plasmalogen phospholipid levels in some tissues from those of certain pathological conditions - including hyperlipidemia and atherosclerosis.

Role of Plasmalogens in the Enhanced Resistance of LDL to Copper-Induced Oxidation After LDL Apheresis

Extracorporeal reduction of plasma low density lipoproteins (LDLs) by LDL apheresis was shown to attenuate the proatherogenic influences of LDL, such as impairment of vasodilation and increased monocyte adhesion to the endothelium. In 16 patients with familial hypercholesterolemia, we analyzed whether LDL apheresis by the heparin precipitation procedure affected the oxidative resistance of LDL. Plasma LDL cholesterol concentrations were reduced by 65% after the apheresis. The lag time of copper-mediated LDL oxidation was increased from 103 to 117 minutes (P<0.0005). The LDL contents of alpha-tocopherol and beta-carotene, as well as the ratio of monounsaturated to polyunsaturated fatty acids in LDL, were not altered. However, the LDL apheresis induced a 15% increase in the LDL contents of plasmalogen phospholipids (P<0.0005), a class of ether phospholipids that were recently shown to prevent lipid oxidation. The phosphatidylcholine (PC) to lysoPC ratio was elevated by 16% after the apheresis (P<0.0005). The percent increase in LDL plasmalogen phospholipids showed a close association with the increased lag time after apheresis (P<0.0005). The LDL plasmalogen contents of the blood samples from patients and from normolipidemic donors were also positively related to the lag time (P<0.005). In vitro loading of LDL with plasmalogen phospholipids resulted in a prolongation of the lag time and an increase in the PC/lysoPC ratio. In conclusion, the rapid rise in LDL contents of plasmalogen phospholipids most probably causes the increase in lag time after LDL apheresis. Plasmalogens appear to play an important role in the oxidation resistance of LDL in vivo.

Pheromone XXX. Identifizierung eines neuartigen Pheromonkomplexes aus der Graseule Scotia exclamationis (Lepidoptera).

Zusammenfassung Mittels Gaschromatographie und GC-Massenspektrometrie wurden (Z)-5-Tetradecenylacetat und (Z)-9-Tetradecenylacetat als Pheromonkomplex bei der Graseule identifiziert.

Plasmalogens as a marker of elevated systemic oxidative stress in Parkinson's disease.

Experimental evidence indicates a significant role of oxidative stress in the pathogenesis of idiopathic Parkinson’s disease (PD). However, some studies report no decrease in common antioxidants in blood plasma as a marker of oxidative stress (1). The aim of this study was to estimate plasmalogen levels in blood plasma samples of patients with PD, a group of 1-alkenyl-2-acyl-sn-glycero-3-phospholipids considered to be a sensitive surrogate marker of oxidative stress. The precise role played by plasmalogen phospholipids of lipoproteins and cell membranes is not well understood. Considerable attention has been focused on the role of plasmalogens as a source of lipid mediators, based on the activity of calcium-independent phospholipase A2 which was shown to catalyze the hydrolysis of arachidonic acid located at the sn2 position of plasmalogens (2). However, plasmalogen status appears to have no influence on stimulated arachidonic acid release in plasmalogendeficient macrophages (3). In addition, plasmalogens can act directly as endogenous antioxidants in defending cell membranes and lipoproteins from reactive radical species. This is accomplished primarily by means of the radical scavenging activity of their vinyl ether bond at the sn1 position (2, 4–6). The present study describes plasmalogen-derived hexadecanal dimethyl acetal (16:0 DMA) concentrations in blood plasma total phospholipid samples from patients with PD, and from age-matched control sub-

Methyl enol ethers as artefacts in capillary gas chromatographic profiles of aldehyde dimethyl acetals.

Methyl enol ethers are detected within the capillary gas chromatographic profiles of aldehyde dimethyl acetals derived from human red cell plasmalogens or from a synthetic aldehyde mixture. They arise from the dimethyl acetals via methanol elimination as artefacts of the injection technique. In a nutritional experiment, the probands showed a rising proportion of dimethyl acetals in the phospholipid fraction of their erythrocyte ghosts; this fact is seen as an effect of the lipid composition of the milk fat administered.

Effective lovastatin therapy in elderly hypercholesterolemic patients — an antioxidative impact?

The effect of 3 months lovastatin therapy on serum lipids, apolipoproteins, alpha-tocopherol and red cell membrane fatty acid pattern was assessed in twelve elderly ambulatory patients (mean age 70.9+/-8.0 years) with hypercholesterolemia type IIa according to Fredrickson. After a run-in period of 4 weeks without drug therapy, the patients were given a daily dose of 20 mg lovastatin. The treatment resulted in statistically significant decreases in mean serum low density lipoprotein cholesterol (LDL-CH, -34%), in the atherogenic index LDL-CH/HDL-CH (-35%) and in the concentration of apolipoprotein B (-26%). No change in the vitamin E status, as related to plasma total lipids, was observed during the 3 months of therapy. The fatty acid pattern of phospholipids from red cell membranes showed an increase in linoleic acid metabolites and a decrease in the precursor linoleic acid, indicating an induction of fatty acid desaturases by lovastatin. In addition, an increase in the plasmalogen portion of erythrocyte membrane phospholipids was exhibited by increases in the proportion of fatty aldehyde dimethyl acetals (DMA) in the fatty acid pattern. The plasmalogens increase may counteract the slow but consistent decrease in their concentration in red cell membranes and human aortas with increasing donor age and in arteriosclerosis. Since plasmalogens may function as physiological antioxidants, the observed increase in DMA concentration might reflect a previously unrecognized antioxidative principle of a lovastatin therapy.