Plasmalogen levels in serum from patients with impaired carbohydrate or lipid metabolism and in elderly subjects with normal metabolic values

https://doi.org/10.1016/S0167-4943(01)00105-4Get rights and content

Abstract

The precise role played by plasmalogen phospholipids (PL) of lipoproteins and cell membranes is not well understood. However, they might act as endogenous antioxidants in defending cell membranes and lipoproteins from reactive oxygen species. A decline of plasmalogen concentrations has been observed in some tissues in normal aging and in some pathologic conditions. For healthy adults, we had reported negative correlations of age with serum plasmalogen PL derived heaxadecanal dimethylacetal (16:0DMA) or octadecanal dimethylacetal (18:0DMA) values. To mark off these age associated changes from disturbances in glucose or lipid metabolism, this study compares the 16:0DMA and 18:0DMA data of serum PL from 118 elderly subjects, aged 57–94 years, and grouped according to the disturbance of glucose or lipid metabolism. Using a new synthetic test mixture of 16:0DMA with oleic acid butylester as a quality control in gas chromatography, the highest 16:0DMA values were found in hypercholesterolemic subjects. However, related to the bulk of serum PL, were the plasmalogens possibly act as antioxidants, the highest values of 16:0DMA/PL were found in controls. A negative correlation of serum triglycerides (TG) with 16:0DMA was detected (n=118). The data suggest a closer association of low DMA values with elevated TG levels as compared to elevated plasma glucose or other serum lipid levels.

Introduction

The phospholipid (PL) class of plasmalogens is ubiquitously found in considerable amounts as a constituent of mammalian cell membranes and of plasma lipoproteins (Horrocks, 1972). Plasmalogens are more susceptible to oxidative reactions, as compared to their fatty acid ester analogues, due to the reactivity of their enolether function (Mangold and Weber, 1987). Some evidence indicates plasmalogens as physiological antioxidants. Also some doubt has been shed on this role of plasmalogens (Zommara et al., 1995). An involvement of plasmalogen PL in HDL-mediated cholesterol efflux from cells has been proposed (Mandel et al., 1998). The biological functions of plasmalogens are not yet established and have been reviewed (Brosche and Platt, 1998, Lee, 1998). Based on the observation of a cytotoxic effect of UV radiation on pyrene-labeled Chinese hamster ovary (CHO) cells deficient in plasmalogens, Zoeller et al. (1988) proposed a role as endogenous antioxidant for plasmalogens. An increased resistance of these cells to UV-cytotoxicity was noted after restoring normal plasmalogen levels (Zoeller et al., 1988).

The chemical structure of plasmalogen PL is characterized by a glycerol backbone which is linked with an fatty aldehyde via an enolether double bond at position sn-1 and is esterified with an fatty acid at position sn-2. The 1-alkenyl structures found in ether lipids of mammalian cells are mainly saturated. Most abundant are hexadecanal dimethylacetal (16:0DMA) and octadecanal dimethylacetal (18:0DMA). Minor amounts of monounsaturated species are present in erythrocyte membranes, but no polyunsaturated ones (Brosche et al., 1985). The fatty alcohol destined to form the 1-alkeny group of ethanolamine plasmalogen is de novo synthesized from acetyl-CoA supplied by peroxisomal beta-oxidation (Hayashi and Hara, 1997). In contrast, the fatty acid pool of plasmalogens contains large portions of polyunsaturated fatty acids of the ω-3 and ω-6 series. Peroxidative and radical chain reactions therefore can involve the enolether function as well as the unsaturated fatty acid moiety (Yavin and Gatt, 1972, Zoeller et al., 1999, Khaselev and Murphy, 2000). An examination of the early phase of oxidative degradation of enol ether and intrachain double bonds by means of 1H-NMR spectroscopy revealed, that in mixtures of polyunsaturated diacyl PL and plasmalogens the oxidation of the intrachain double bond of ester PL is considerably delayed, while the enol ether double bond is rapidly degraded (Reiss et al., 1997).

Buddecke and Andresen (1959) reported a decline in the plasmalogen content of normal and even more pronounced of arteriosclerotic aortas with increasing donor age. Since plasmalogens probably are physiological antioxidants, these observations support the ‘oxidation hypothesis’ of arteriosclerosis and the free radical theory of aging (Harman, 1956). In aging the plasmalogen content of plasma and red cell membrane ghosts seems to be reduced (Brosche, 1997).

To mark off these age associated alterations in healthy adults from disturbances in glucose and lipid metabolism, this study compares the serum PL plasmalogen-derived fatty aldehyde dimethyl acetal (DMA) data of 118 elderly subjects with disturbed glucose and lipid metabolism with controls. If lower PL plasmalogen levels are considered as a sign of increased risk of oxidative burden, this condition is marked strongly in the subjects with elevated serum triglyceride (TG) values. The data suggest a closer association of low DMA values with elevated serum TG levels, as compared to elevated plasma glucose or other serum lipid levels.

Section snippets

Subjects

Blood lipid fractions and plasmalogen levels were studied in 118 elderly subjects, aged 57.1–94.6 years. According to the diagnosis or to metabolic parameters seven groups were formed: (I) subjects with an impaired oral glucose tolerance, as revealed 2 h after a test load with 100 g glucose, given with tea (IOGTT-group); (II) patients with insulin dependent diabetes mellitus (IDDM-group); (III) patients with non-insulin dependent diabetes mellitus (NIDDM-group); (IV) patients with

Results

Table 2 gives the mean values with standard deviations of plasma glucose and of serum lipid fractions from the seven groups of subjects formed. As a consequence of forming the groups, the patients with diabetes mellitus (II and III) have the highest glucose values. The mean glucose level is in the upmost part of the normal range (up to 115 mg/dl) in the group of subjects with an impaired OGTT (I). Then the levels drop in the sequence VI, V, VII and IV. Evidently the LDL-CH values are highest in

Discussion

The precise role played by plasmalogens in lipoproteins and in cell membranes is not well understood. However, some evidence indicates that the in vitro antioxidative properties of these molecules (Engelmann et al., 1994, Jürgens et al., 1995, Hahnel et al., 1999) also are effective in vivo (Brosche and Platt, 1998, Lee, 1998), protecting cell membranes and lipoproteins from reactive oxygen species. Considerable amounts of plasmenylethanolamine have been detected in lipoproteins secreted by

Acknowledgements

Part of this work was supported by a grant from the Willy-Pitzer-Stiftung, Bad Nauheim. Thanks are also due to Dr Hartmut Eicher, Institute of Gerontology, University of Erlangen-Nürnberg, for providing the computer program STAN PLUS, and to all of the medical staff of the Medizinische Klinik 2, Klinikum Nürnberg, engaged in obtaining the blood samples.

References (26)

Cited by (19)

  • Dysfunctional plasmalogen dynamics in the plasma and platelets of patients with schizophrenia

    2015, Schizophrenia Research
    Citation Excerpt :

    While our study did not include prodromal patients, our data clearly support the findings of Kaddurah-Daouk et al. in medicated patients. Since metabolic syndrome is prevalent in schizophrenics and is invoked or amplified by treatment with antipsychotics (Malhotra et al., 2013), this is a complicating feature that needs to be carefully assessed in future studies of larger cohorts of patients with schizophrenia since metabolic syndrome also is associated with decreased plasmalogen levels (Brosche, 2001; Kaddurah-Daouk et al., 2007). However, since plasmalogen decrements have been demonstrated in first-onset patients, it appears that there may be an intrinsic metabolic defect affecting plasmalogen levels that might be amplified by the development of metabolic syndrome.

  • Reduced plasmalogen concentration as a surrogate marker of oxidative stress in elderly septic patients

    2013, Archives of Gerontology and Geriatrics
    Citation Excerpt :

    The Bavarian Red Cross Blood Donor BioBank (Wiesentheid, Germany) provided EDTA-plasma samples from healthy age- and sex matched controls. Plasmalogens were analyzed essentially as has been described before (Brosche, 2001). Briefly, the lipids of lyophilized samples of 0.5 mL EDTA plasma were extracted and fractionated into lipid classes on silica columns.

  • Plasmalogens the neglected regulatory and scavenging lipid species

    2011, Chemistry and Physics of Lipids
    Citation Excerpt :

    In these subjects plasmalogens as a marker for the level of oxidative stress were at the same time depleted in erythrocyte membranes and predictive for cardiovascular mortality (Stenvinkel et al., 2004). On the other hand hypercholesterolemia has also been found to influence plasmalogen levels, with highest values of 16:0 plasmalogen-derived dimethylacetal (DMA) in the hypercholesterolemic group (Brosche, 2001). Another hint for the importance of plasmalogens in inflammatory processes was obtained in hypercholesterolemic patients treated with simvastatin.

View all citing articles on Scopus
View full text