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1

Rothhaar, Tatjana L., Sven Grösgen, Viola J. Haupenthal та ін. "Plasmalogens Inhibit APP Processing by Directly Affectingγ-Secretase Activity in Alzheimer’s Disease". Scientific World Journal 2012 (2012): 1–15. http://dx.doi.org/10.1100/2012/141240.

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Lipids play an important role as risk or protective factors in Alzheimer’s disease (AD). Previously it has been shown that plasmalogens, the major brain phospholipids, are altered in AD. However, it remained unclear whether plasmalogens themselves are able to modulate amyloid precursor protein (APP) processing or if the reduced plasmalogen level is a consequence of AD. Here we identify the plasmalogens which are altered in human ADpostmortembrains and investigate their impact on APP processing resulting in Aβ production. All tested plasmalogen species showed a reduction in γ-secretase activity whereas β- and α-secretase activity mainly remained unchanged. Plasmalogens directly affected γ-secretase activity, protein and RNA level of the secretases were unaffected, pointing towards a direct influence of plasmalogens on γ-secretase activity. Plasmalogens were also able to decrease γ-secretase activity in humanpostmortemAD brains emphasizing the impact of plasmalogens in AD. In summary our findings show that decreased plasmalogen levels are not only a consequence of AD but that plasmalogens also decrease APP processing by directly affecting γ-secretase activity, resulting in a vicious cycle: Aβ reduces plasmalogen levels and reduced plasmalogen levels directly increase γ-secretase activity leading to an even stronger production of Aβ peptides.
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2

Engelmann, B. "Plasmalogens: targets for oxidants and major lipophilic antioxidants." Biochemical Society Transactions 32, no. 1 (2004): 147–50. http://dx.doi.org/10.1042/bst0320147.

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Cellular membranes and plasma lipoproteins are less efficiently protected against oxidative stress than the various aqueous compartments of mammalian organisms. Here, previous results on the role of plasmalogens in lipid oxidation are evaluated on the basis of criteria required for an antioxidant. The plasmalogen-specific enol ether double bond is targeted by a vast variety of oxidants, including peroxyl radicals, metal ions, singlet oxygen and halogenating species. Oxidation of the vinyl ether markedly prevents the oxidation of highly polyunsaturated fatty acids, and products of plasmalogen degradation do not propagate lipid oxidation. This protection is also demonstrated intramolecularly, thus ascertaining the function of plasmalogens as a major storage pool for polyunsaturated fatty acids. Although cells rapidly incorporate and synthesize plasmalogens de novo, their plasmalogen contents can be deliberately increased by supplementation with precursors. Thus plasmalogens terminate lipid-oxidation processes, are present in adequate locations at sufficient concentrations, and are rapidly regenerated, classifying them as efficient antioxidants in vitro. Future work should address the in vivo role of plasmalogens in lipid oxidation and the biological function of plasmalogen interactions with oxidants.
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3

Paul, Sudip, Aliki A. Rasmiena, Kevin Huynh, et al. "Oral Supplementation of an Alkylglycerol Mix Comprising Different Alkyl Chains Effectively Modulates Multiple Endogenous Plasmalogen Species in Mice." Metabolites 11, no. 5 (2021): 299. http://dx.doi.org/10.3390/metabo11050299.

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Plasmalogens or alkenylphospholipids are a sub-class of glycerophospholipids with numerous biological functions and are thought to have protective effects against metabolic disease. Dietary supplementation with alkylglycerols (AKGs) has been shown to increase endogenous plasmalogen levels, however effective modulation of different molecular plasmalogen species has not yet been demonstrated. In this study, the effects of an orally-administered AKG mix (a mixture of chimyl, batyl and selachyl alcohol at a 1:1:1 ratio) on plasma and tissue lipids, including plasmalogens, was evaluated. Mice on a Western-type diet were treated with either an AKG mix or vehicle (lecithin) for 1, 2, 4, 8 and 12 weeks. Treatment with the AKG mix significantly increased the total plasmalogen content of plasma, liver and adipose tissue as a result of elevations in multiple plasmalogen species with different alkenyl chains. Alkylphospholipids, the endogenous precursors of plasmalogens, showed a rapid and significant increase in plasma, adipose tissue, liver and skeletal muscle. A significant accumulation of alkyl-diacylglycerol and lyso-ether phospholipids was also observed in plasma and tissues. Additionally, the dynamics of plasmalogen-level changes following AKG mix supplementation differed between tissues. These findings indicate that oral supplementation with an AKG mix is capable of upregulating and maintaining stable expression of multiple molecular plasmalogen species in circulation and tissues.
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4

Wu, Yue, Zhen Chen, Jiaping Jia, Hitoshi Chiba, and Shu-Ping Hui. "Quantitative and Comparative Investigation of Plasmalogen Species in Daily Foodstuffs." Foods 10, no. 1 (2021): 124. http://dx.doi.org/10.3390/foods10010124.

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Plasmalogens are an animal-derived functional phospholipid increasingly known as a safe and effective nutritional ingredient, however, the quantitation and comparison of plasmalogen species in foods is limited. In the present work, determination methods for dietary plasmalogens using liquid chromatography-tandem mass spectroscopy under positive and negative ionization modes were compared. The negative-mode method, which showed better selectivity, sensitivity, and accuracy, was then applied in 14 kinds of livestock, poultry, and seafood samples. Livestock and poultry showed abundant total plasmalogen (530.83–944.94 nmol/g), higher than fish (46.08–399.75 nmol/g) and mollusk (10.00–384.76 nmol/g). While fish and mollusk samples expressed healthier fatty acyl composition, with higher eicosapentaenoyl and more beneficial n-6/n-3 ratio than the land animal meats, especially for squid and octopus, with eicosapentaenoyl of 98.4% and 94.5%, respectively. The correlations among plasmalogen species varied in different foodstuffs with distinguishing patterns, suggesting the customizable strategies for achieving targeted plasmalogen species. These findings not only provided fundamental comparison of plasmalogen among daily foodstuffs, but also contributed to extend the dietary plasmalogen sources for health food development.
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5

Wu, Yue, Zhen Chen, Jiaping Jia, Hitoshi Chiba, and Shu-Ping Hui. "Quantitative and Comparative Investigation of Plasmalogen Species in Daily Foodstuffs." Foods 10, no. 1 (2021): 124. http://dx.doi.org/10.3390/foods10010124.

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Plasmalogens are an animal-derived functional phospholipid increasingly known as a safe and effective nutritional ingredient, however, the quantitation and comparison of plasmalogen species in foods is limited. In the present work, determination methods for dietary plasmalogens using liquid chromatography-tandem mass spectroscopy under positive and negative ionization modes were compared. The negative-mode method, which showed better selectivity, sensitivity, and accuracy, was then applied in 14 kinds of livestock, poultry, and seafood samples. Livestock and poultry showed abundant total plasmalogen (530.83–944.94 nmol/g), higher than fish (46.08–399.75 nmol/g) and mollusk (10.00–384.76 nmol/g). While fish and mollusk samples expressed healthier fatty acyl composition, with higher eicosapentaenoyl and more beneficial n-6/n-3 ratio than the land animal meats, especially for squid and octopus, with eicosapentaenoyl of 98.4% and 94.5%, respectively. The correlations among plasmalogen species varied in different foodstuffs with distinguishing patterns, suggesting the customizable strategies for achieving targeted plasmalogen species. These findings not only provided fundamental comparison of plasmalogen among daily foodstuffs, but also contributed to extend the dietary plasmalogen sources for health food development.
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6

Rüstow, B., I. Kolleck, F. Guthmann, R. Haupt, D. Kunze, and P. Stevens. "Synthesis and secretion of plasmalogens by type-II pneumocytes." Biochemical Journal 302, no. 3 (1994): 665–68. http://dx.doi.org/10.1042/bj3020665.

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Alveolar surfactant (exposed to air and therefore a prime target of air oxidants) is supplied with antioxidants during its intracellular formation on type-II pneumocytes [Rüstow, Haupt, Stevens and Kunze (1993) Am. J. Physiol. 265, L133-L139]. Plasmalogens can protect animal cells against lipid peroxidation caused by u.v. radiation. It has been suggested that plasmalogens play a direct role in protecting animal cell membranes against oxidative stress [Zoeller, Morand and Raetz (1988) J. Biol. Chem. 263, 11590-11596]. We investigated biosynthesis and secretion of plasmalogens and phospholipids by type-II cells of adult rat lungs. The plasmalogens of type-II cells consist of 93% ethanolamine plasmalogens (EthPlas) and 7% choline plasmalogens (ChoPlas). Plasmalogens isolated from alveolar surfactant, however, consist of 36.5% ChoPlas and 63.5% EthPlas. The different incorporation rates of [14C]hexadecanol into both types of plasmalogen by type-II pneumocytes are reflected in the relative proportions of their total cellular plasmalogen content. Type-II cells cultured in the presence of labelled hexadecanol or labelled hexadecylglycerol and of labelled palmitate secrete labelled ChoPlas and labelled phospholipids, both spontaneously and in response to isoprenaline. The spontaneous and stimulated secretion rates of labelled ChoPlas are 3-6 times higher than those of labelled EthPlas. This higher relative secretion rate of ChoPlas corresponds to its higher proportion in the total plasmalogen content of alveolar surfactant compared with type-II cells. Added extracellular surfactant-specific protein A inhibits the secretion of plasmalogens as well as that of phospholipids by type-II cells. The molecular species of EthPlas and ChoPlas isolated from type-II cells or lung lavage do not differ significantly and consist mainly of molecular species containing poly-unsaturated fatty acids. We conclude that ChoPlas are secreted partly as integral constituents of the alveolar surfactant. Type-II cells select between both types of plasmalogens for secretion as a constituent of surfactant. The intramolecular sorting signal presumably is the choline moiety.
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7

Cook, Harold W., Susan E. Thomas, and Zhaolin Xu. "Essential fatty acids and serine as plasmalogen precursors in relation to competing metabolic pathways." Biochemistry and Cell Biology 69, no. 7 (1991): 475–84. http://dx.doi.org/10.1139/o91-071.

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Interest in altered ether-lipid metabolism, associated with peroxisomal disorders including adrenoleukodystrophy and Zellweger's syndrome, has highlighted present limitations in our understanding of the biosynthesis and turnover of plasmalogens. These 1-alkenyl ethanolamine phosphoglycerides are major phospholipids in brain, vascular tissue, neutrophils, and most tumors, and they constitute 15–20% of total phospholipids in cultured glioma cells. In glioma, turnover of polyunsaturated acyl chains in the sn-2 position of plasmalogens was examined in relation to selectivity for the (n–3) and (n–6) families. Remodeling of acyl chains was more dependent on chain length than on selectivity between families, consistent with plasmalogens enriched in polyunsaturated, but not specifically (n–3), fatty acids. Extracellular serine was a precursor of serine and ethanolamine phosphoglycerides and was associated with plasmalogens due to decarboxylation and headgroup exchange. Incorporation of extracellular serine ceased within 8 h, even though more than 50% of the label remained in the medium. Analyses of medium and cellular water-soluble components indicated rapid conversion of serine to glycine and other metabolites not used in phospholipid biosynthesis. Thus, nutrient molecules as precursors of plasmalogens are involved in complex competitive interactions. As functions of plasmalogens are clarified, regulation of plasmalogen turnover becomes an increasingly important issue and elucidation of these processes is essential.Key words: plasmalogen, serine, fatty acids, glioma.
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8

Rüdiger, M., I. Kolleck, G. Putz, R. R. Wauer, P. Stevens, and B. Rüstow. "Plasmalogens effectively reduce the surface tension of surfactant-like phospholipid mixtures." American Journal of Physiology-Lung Cellular and Molecular Physiology 274, no. 1 (1998): L143—L148. http://dx.doi.org/10.1152/ajplung.1998.274.1.l143.

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The alkenyl-acyl subclass of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (plasmalogens) are minor components of alveolar surfactant. Plasmalogens promote and stabilize hexagonal structures of phospholipids. In another study (W. R. Perkins, R. B. Dause, R. A. Parente, S. R. Michey, K. C. Neuman, S. M. Gruner, T. F. Taraschi, and A. S. Janoff. Science 273: 330–332, 1996), it was shown that polymorphic phase behavior may have an important role in the effective functioning of pulmonary surfactant. Therefore, we hypothesized that surface properties of phospholipid mixtures that contain plasmalogens are superior to plasmalogen-free mixtures. The effect of plasmalogens on surface tension of surfactant-like phospholipid mixtures (70 mol% dipalmitoyl phosphatidylcholine, 10 mol% phosphatidylglycerol, and 20 mol% PtdEtn) was measured. Using the pulsating bubble surfactometer, we show that an increasing amount of ethanolamine plasmalogens [plasmenylethanolamine (PlsEtn)] results in reduction of surface tension (0 mol% PlsEtn 44.7 ± 1.7, 2 mol% 33.5 ± 1.7, 4 mol% 36 ± 3.1, 6 mol% 26.2 ± 2.9, and 8 mol% 22.2 ± 0.3 mN/m). By means of the captive bubble surfactometer, minimal surface tension reached with 8 mol% PlsEtn was even lower (3.8 ± 0.7 mN/m). With regard to morphological studies (B. Fringes, K. Gorgas, and A. Reith. Eur. J. Cell Biol. 46: 136–143, 1988), clofibrate treatment of rats might increase the plasmalogen content of alveolar surfactant. However, in the present study, we could not show that synthesis and secretion of plasmalogens are affected by clofibrate treatment.
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9

Gallego-García, Aránzazu, Antonio J. Monera-Girona, Elena Pajares-Martínez, et al. "A bacterial light response reveals an orphan desaturase for human plasmalogen synthesis." Science 366, no. 6461 (2019): 128–32. http://dx.doi.org/10.1126/science.aay1436.

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Plasmalogens are glycerophospholipids with a hallmark sn-1 vinyl ether bond. These lipids are found in animals and some bacteria and have proposed membrane organization, signaling, and antioxidant roles. We discovered the plasmanylethanolamine desaturase activity that is essential for vinyl ether bond formation in a bacterial enzyme, CarF, which is a homolog of the human enzyme TMEM189. CarF mediates light-induced carotenogenesis in Myxococcus xanthus, and plasmalogens participate in sensing photooxidative stress through singlet oxygen. TMEM189 and other animal homologs could functionally replace CarF in M. xanthus, and knockout of TMEM189 in a human cell line eliminated plasmalogens. Discovery of the human plasmanylethanolamine desaturase will spur further study of plasmalogen biogenesis, functions, and roles in disease.
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10

Werner, Ernst R., Markus A. Keller, Sabrina Sailer, et al. "TheTMEM189gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens." Proceedings of the National Academy of Sciences 117, no. 14 (2020): 7792–98. http://dx.doi.org/10.1073/pnas.1917461117.

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A significant fraction of the glycerophospholipids in the human body is composed of plasmalogens, particularly in the brain, cardiac, and immune cell membranes. A decline in these lipids has been observed in such diseases as Alzheimer’s and chronic obstructive pulmonary disease. Plasmalogens contain a characteristic 1-O-alk-1′-enyl ether (vinyl ether) double bond that confers special biophysical, biochemical, and chemical properties to these lipids. However, the genetics of their biosynthesis is not fully understood, since no gene has been identified that encodes plasmanylethanolamine desaturase (E.C. 1.14.99.19), the enzyme introducing the crucial alk-1′-enyl ether double bond. The present work identifies this gene as transmembrane protein 189 (TMEM189). Inactivation of theTMEM189gene in human HAP1 cells led to a total loss of plasmanylethanolamine desaturase activity, strongly decreased plasmalogen levels, and accumulation of plasmanylethanolamine substrates and resulted in an inability of these cells to form labeled plasmalogens from labeled alkylglycerols. Transient expression of TMEM189 protein, but not of other selected desaturases, recovered this deficit. TMEM189 proteins contain a conserved protein motif (pfam10520) with eight conserved histidines that is shared by an alternative type of plant desaturase but not by other mammalian proteins. Each of these histidines is essential for plasmanylethanolamine desaturase activity. Mice homozygous for an inactivatedTmem189gene lacked plasmanylethanolamine desaturase activity and had dramatically lowered plasmalogen levels in their tissues. These results assign theTMEM189gene to plasmanylethanolamine desaturase and suggest that the previously characterized phenotype ofTmem189-deficient mice may be caused by a lack of plasmalogens.
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11

Zoeller, Raphael A., Todd J. Grazia, Peter LaCamera, James Park, Daniel P. Gaposchkin, and Harrison W. Farber. "Increasing plasmalogen levels protects human endothelial cells during hypoxia." American Journal of Physiology-Heart and Circulatory Physiology 283, no. 2 (2002): H671—H679. http://dx.doi.org/10.1152/ajpheart.00524.2001.

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Supplementation of cultured human pulmonary arterial endothelial cells (PAEC) with sn-1- O-hexadecylglycerol (HG) resulted in an approximately twofold increase in cellular levels of plasmalogens, a subclass of phospholipids known to have antioxidant properties; this was due, primarily, to a fourfold increase in the choline plasmalogens. Exposure of unsupplemented human PAEC to hypoxia (Po 2 = 20–25 mmHg) caused an increase in cellular reactive oxygen species (ROS) over a period of 5 days with a coincident decrease in viability. In contrast, HG-supplemented cells survived for at least 2 wk under these conditions with no evidence of increased ROS. Hypoxia resulted in a selective increase in the turnover of the plasmalogen plasmenylethanolamine. Human PAEC with elevated plasmalogen levels were also more resistant to H2O2, hyperoxia, and the superoxide generator plumbagin. This protection was seemingly specific to cellular stresses in which significant ROS were generated because the sensitivity to lethal heat shock or glucose deprivation was not altered in HG-treated human PAEC. HG, by itself, was not sufficient for protection; HG supplementation of bovine PAEC had no effect upon plasmalogen levels and did not rescue these cells from the cytotoxic effects of hypoxia. This is the initial demonstration that plasmalogen content can be substantially enhanced in a normal cell. These data also demonstrate that HG can protect cells during hypoxia and other ROS-mediated stress, likely due to the resulting increase in these antioxidant phospholipids.
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12

Arthur, G., L. Page, T. Mock, and P. C. Choy. "The catabolism of plasmenylcholine in the guinea pig heart." Biochemical Journal 236, no. 2 (1986): 475–80. http://dx.doi.org/10.1042/bj2360475.

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The hydrolysis of the alkenyl bonds of plasmenylcholine and plasmenylethanolamine by plasmalogenase, followed by hydrolysis of the resultant lysophospholipid by lysophospholipase, has been postulated as the major pathway for the catabolism of these plasmalogens. However, the postulation was based solely on the presence of plasmalogenase activity towards plasmenylethanolamine and plasmenylcholine in the brain. In this study we have demonstrated the absence of plasmalogenase activity for plasmenylcholine in the guinea pig heart under a wide range of experimental conditions. Plasmenylcholine was hydrolysed by phospolipase A2 activities in cardiac microsomal, mitochondrial and cytosolic fractions. Phospholipase A2 activities in these fractions had an alkaline pH optimum and were enhanced by Ca2+. The enzymes also displayed high specificity for plasmenylcholine with linoleoyl or oleoyl at the C-2 position. Lysoplasmalogenase activity for lysoplasmenycholine was also detected and characterized in the microsomal and mitochondrial fractions. Since the cardiac plasmalogenase is only active towards plasmenylethanolamine but not plasmenylcholine, the catabolism of these two plasmalogens must be different from each other. We postulate that the major pathway for the catabolism of plasmenycholine involves the hydrolysis of the C-2 fatty acid by phospholipase A2, and hydrolysis of the vinyl ether group of the resultant lysoplasmenylcholine by lysoplasmalogenase.
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13

Scheick, Cordula, and Gerhard Spiteller. "Bildung von Enolether-Epoxiden durch Einwirkung von (9S,10E,12Z)-Hydroperoxyoctadecadiensäure auf Plasmalogene." Liebigs Annalen der Chemie 1993, no. 12 (1993): 1245–48. http://dx.doi.org/10.1002/jlac.1993199301202.

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14

NAGAN, Narasimhan, Amiya K. HAJRA, Leslie K. LARKINS, et al. "Isolation of a Chinese hamster fibroblast variant defective in dihydroxyacetonephosphate acyltransferase activity and plasmalogen biosynthesis: use of a novel two-step selection protocol." Biochemical Journal 332, no. 1 (1998): 273–79. http://dx.doi.org/10.1042/bj3320273.

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We have developed a two-step selection protocol to generate a population of Chinese hamster ovary (CHO) cell variants that are plasmalogen-deficient, but contain intact, functional peroxisomes (plasmalogen-/peroxisome+). This involved sequential exposures of a mutagenized cell population to photodynamic damage by using two different pyrene-labelled sensors, 9-(1´-pyrene)nonanol and 12-(1´-pyrene)dodecanoic acid. By this procedure we generated several isolates, all except one of which displayed a severe decrease in plasmalogen biosynthesis. Further characterization of one of the plasmalogen-deficient isolates, NRel-4, showed that it contained intact, functional peroxisomes. Whole-cell homogenates from NRel-4 displayed severely decreased dihydroxyacetone phosphate acyltransferase, which catalyses the first step in plasmalogen biosynthesis. NRel-4 and another, recently described, plasmalogen-deficient cell line, NZel-1 [Nagan, Hajra, Das, Moser, Moser, Lazarow, Purdue and Zoeller (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 4475–4480] were hypersensitive to singlet oxygen, supporting the notion of plasmalogens as radical oxygen scavengers. Wild-type-like resistance could be conferred on NRel-4 upon restoration of plasmalogen content by supplementation with a bypass compound, sn-1-hexadecylglycerol. NRel-4 and other plasmalogen-/peroxisome+ strains will allow us to examine further the role of ether lipids in cellular functions without complications associated with peroxisome deficiency, and might serve as an animal cell model for certain forms of the human genetic disorder rhizomelic chondrodysplasia punctata.
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15

Arthur, G., and L. Page. "Synthesis of phosphatidylethanolamine and ethanolamine plasmalogen by the CDP-ethanolamine and decarboxylase pathways in rat heart, kidney and liver." Biochemical Journal 273, no. 1 (1991): 121–25. http://dx.doi.org/10.1042/bj2730121.

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Studies with mammalian cell lines have led to suggestions that mammalian tissues may derive all of their phosphatidylethanolamine (PE) from the decarboxylation of phosphatidylserine (PS), and also that the physiological significance of the CDP-ethanolamine pathway was the synthesis of ethanolamine plasmalogen. We have therefore investigated the biosynthesis of PE and ethanolamine plasmalogen via the CDP-ethanolamine and decarboxylation pathways in vivo in three rat tissues (heart, kidney and liver), which differ in ethanolamine plasmalogen content. In all three tissues [14C]ethanolamine was incorporated into both PE and ethanolamine plasmalogen, whereas [3H]serine was incorporated into only PS and PE fractions. When [14C]ethanolamine was introduced into the animals, the specific radioactivity of ethanolamine plasmalogen in the kidney was always greater than that of the PE fraction; in the heart the specific radioactivity of the ethanolamine plasmalogen fraction was similar to that of the PE fraction, whereas in the liver the specific radioactivity of the PE fraction was always greater than that of the ethanolamine plasmalogen fraction. The results obtained in this study indicate that: (1) the CDP-ethanolamine pathway is utilized for the synthesis of both PE and ethanolamine plasmalogen in all three tissues; (2) the decarboxylation pathway is utilized solely for the synthesis of PE; (3) serine plasmalogens are not formed by base-exchange reactions; (4) the relative utilization of the CDP-ethanolamine pathway for the synthesis of PE and ethanolamine plasmalogen varies among tissues. Our studies also revealed that the hypolipidaemic drug MDL 29350 is a potent inhibitor of PE N-methyltransferase activity in vitro and in vivo.
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16

Rüdiger, Mario, Angelika Tölle, Wolfgang Meier, and Bernd Rüstow. "Naturally derived commercial surfactants differ in composition of surfactant lipids and in surface viscosity." American Journal of Physiology-Lung Cellular and Molecular Physiology 288, no. 2 (2005): L379—L383. http://dx.doi.org/10.1152/ajplung.00176.2004.

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Pulmonary surfactant biophysical properties are best described by surface tension and surface viscosity. Besides lecithin, surfactant contains a variety of minor lipids, such as plasmalogens, polyunsaturated fatty acid-containing phospholipids (PUFA-PL), and cholesterol. Plasmalogens and cholesterol improve surface properties of lipid mixtures significantly. High PUFA-PL and plasmalogen content in tracheal aspirate of preterm infants reduces the risk of developing chronic lung disease. Different preparations are available for exogenous surfactant substitution; however, little is known about lipid composition and surface viscosity. Thus lipid composition and surface properties (measured by oscillating drop surfactometer) of three commercial surfactant preparations (Alveofact, Curosurf, Survanta) were compared. Lipid composition exhibited strong differences: Survanta had the highest proportion of disaturated PL and total neutral lipids and the lowest proportion of PUFA-PL. Highest plasmalogen and PUFA-PL concentrations were found in Curosurf (3.8 ± 0.1 vs. 26 ± 1 mol%) compared with Alveofact (0.9 ± 0.3 vs. 11 ± 1) and Survanta (1.5 ± 0.2 vs. 6 ± 1). In Survanta samples, viscosity increased >8 × 10−6 kg/s at surface tension of 30 mN/m. Curosurf showed only slightly increased surface viscosity below surface tensions of 25 mN/m, and viscosity did not reach 5 × 10−6 kg/s. By adding defined PL to Survanta, we obtained a Curosurf-like lipid mixture (without plasmalogens) that exhibited biophysical properties like Curosurf. Different lipid compositions could explain some of the differences in surface viscosity. Therefore, PL pattern and minor surfactant lipids are important for biophysical activity and should be considered when designing synthetic surfactant preparations.
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HAHNEL, Daniela, Thomas HUBER, Volker KURZE, Klaus BEYER, and Bernd ENGELMANN. "Contribution of copper binding to the inhibition of lipid oxidation by plasmalogen phospholipids." Biochemical Journal 340, no. 2 (1999): 377–83. http://dx.doi.org/10.1042/bj3400377.

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The role of plasmalogen phospholipids for copper-induced lipid oxidation was evaluated. Using 1H-NMR we observed that the copper (CuSO4)-promoted oxidative degradation of polyunsaturated fatty acids in micellar solution was dose-dependently attenuated by the plasmalogen lysoplasmenylethanolamine from bovine brain (lysoBP-PtdEtn). This was due to a direct interaction of copper ions with the plasmalogen-specific enol ether double bond. The enol ether methine 1H signal decreased on the addition of copper, saturation being reached at a molar ratio of lysoBP-PtdEtn to copper of 1:1. The original 1H signal was recovered almost completely after the addition of EDTA. Enrichment of micelles and low-density lipoproteins (LDLs) with plasmalogen phospholipids led to a decrease in the Cu(II) concentration in the aqueous media. After loading of LDLs in vitro with BP-PtdEtn, the LDL-dependent formation of Cu(I) was decreased, in particular in particles experimentally supplemented with α-tocopherol. The suppression of copper-promoted lipid oxidation that was observed in the presence of plasmalogen phospholipids plus α-tocopherol was greater than the sum of the protective effects elicited by the two substances alone. In conclusion, the formation of a complex between copper ions and the plasmalogens accounts partly for their inhibition of copper-induced lipid oxidation.
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18

Loidl-Stahlhofen, A., K. Hannemann, R. Felde та G. Spiteller. "Epoxidation of plasmalogens: source for long-chain α-hydroxyaldehydes in subcellular fractions of bovine liver". Biochemical Journal 309, № 3 (1995): 807–12. http://dx.doi.org/10.1042/bj3090807.

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1. Masked long-chain alpha-hydroxyaldehydes were trapped in all subcellular fractions of bovine liver by application of pentafluorbenzyloxime derivatization [van Kuijk, Thomas, Stephens and Dratz (1986) Biochem. Biophys. Res. Commun. 139, 144-149] and quantified via GLC/MS using characteristic ion traces. 2. The chain-length profile of long-chain 2-hydroxyalkanales clearly indicates their relationship to plasmalogens as precursor molecules. 3. The previously postulated existence of alpha-acyloxyplasmalogens as precursor molecules of masked long-chain alpha-hydroxyaldehydes in bovine tissue lipids [Lutz and Spiteller (1991) Liebigs Ann. Chem. 1991, 563-567] was excluded. 4. The constant oxidation rate of plasmalogens in all subcellular fractions provides conclusive evidence for a non-enzymic plasmalogen epoxidation process (probably via hydroperoxy radicals). 5. The high reactivity of alpha-hydroxyaldehydes sheds some doubt on the postulation that plasmalogens protect mammalian cells against oxidative stress as postulated previously [Morand, Zoeller and Raetz (1988) J. Biol. Chem. 263, 11590-11596; Morand, Zoeller and Raetz (1988) J. Biol. Chem. 263, 11597-11606].
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19

Heinle, Helmut, Nadja Gugeler, Roswitha Felde, Dagmar Okech, and Gerhard Spiteller. "Oxidation of Plasmalogens Produces Highly Effective Modulators of Macrophage Function." Zeitschrift für Naturforschung C 55, no. 1-2 (2000): 115–20. http://dx.doi.org/10.1515/znc-2000-1-221.

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Abstract Model derivatives of plasmalogens and chemically synthesized oxidative degradation products as found e.g. during oxidation of low density lipoproteins show strong effects on phagocytosis induced secretion of reactive oxygen species of macrophages which was measured by luminol-enhanced chemiluminescence. Whereas a plasmalogen epoxide showed enhancing effects in submicromolar range, inhibition was found with higher concentrations as well as with a-hydroxyaldehydes. The substances showed only little effects on the non-cellular ROSdependent chemiluminescence of the reaction between hydrogen peroxide and opsonized zymosan and no cytotoxic effects under the assay conditions used. These results show that oxidative modification and degradation of plasmalogens occuring also under pathophysiological situations in vivo produces effective modulators of macrophage function which could be important; e.g. during inflammation or atherogenesis.
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Honsho, Masanori, Fabian Dorninger, Yuichi Abe, et al. "Impaired plasmalogen synthesis dysregulates liver X receptor-dependent transcription in cerebellum." Journal of Biochemistry 166, no. 4 (2019): 353–61. http://dx.doi.org/10.1093/jb/mvz043.

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Abstract Synthesis of ethanolamine plasmalogen (PlsEtn) is regulated by modulating the stability of fatty acyl-CoA reductase 1 (Far1) on peroxisomal membrane, a rate-limiting enzyme in plasmalogen synthesis. Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis in cultured cells by altering the stability of squalene epoxidase (SQLE). However, regulation of PlsEtn synthesis and physiological consequences of plasmalogen homeostasis in tissues remain unknown. In the present study, we found that the protein but not the transcription level of Far1 in the cerebellum of the Pex14 mutant mouse expressing Pex14p lacking its C-terminal region (Pex14ΔC/ΔC) is higher than that from wild-type mouse, suggesting that Far1 is stabilized by the lowered level of PlsEtn. The protein level of SQLE was increased, whereas the transcriptional activity of the liver X receptors (LXRs), ligand-activated transcription factors of the nuclear receptor superfamily, is lowered in the cerebellum of Pex14ΔC/ΔC and the mice deficient in dihydroxyacetonephosphate acyltransferase, the initial enzyme for the synthesis of PlsEtn. These results suggest that the reduction of plasmalogens in the cerebellum more likely compromises the cholesterol homeostasis, thereby reducing the transcriptional activities of LXRs, master regulators of cholesterol homeostasis.
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Lebrero, Patricia, Alma M. Astudillo, Julio M. Rubio та ін. "Cellular Plasmalogen Content Does Not Influence Arachidonic Acid Levels or Distribution in Macrophages: A Role for Cytosolic Phospholipase A2γ in Phospholipid Remodeling". Cells 8, № 8 (2019): 799. http://dx.doi.org/10.3390/cells8080799.

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Availability of free arachidonic acid (AA) constitutes a rate limiting factor for cellular eicosanoid synthesis. AA distributes differentially across membrane phospholipids, which is largely due to the action of coenzyme A-independent transacylase (CoA-IT), an enzyme that moves the fatty acid primarily from diacyl phospholipid species to ether-containing species, particularly the ethanolamine plasmalogens. In this work, we examined the dependence of AA remodeling on plasmalogen content using the murine macrophage cell line RAW264.7 and its plasmalogen-deficient variants RAW.12 and RAW.108. All three strains remodeled AA between phospholipids with similar magnitude and kinetics, thus demonstrating that cellular plasmalogen content does not influence the process. Cell stimulation with yeast-derived zymosan also had no effect on AA remodeling, but incubating the cells in AA-rich media markedly slowed down the process. Further, knockdown of cytosolic-group IVC phospholipase A2γ (cPLA2γ) by RNA silencing significantly reduced AA remodeling, while inhibition of other major phospholipase A2 forms such as cytosolic phospholipase A2α, calcium-independent phospholipase A2β, or secreted phospholipase A2 had no effect. These results uncover new regulatory features of CoA-IT-mediated transacylation reactions in cellular AA homeostasis and suggest a hitherto unrecognized role for cPLA2γ in maintaining membrane phospholipid composition via regulation of AA remodeling.
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ZOELLER, Raphael A., Andrew C. LAKE, Narasimhan NAGAN, Daniel P. GAPOSCHKIN, Margaret A. LEGNER, and Wilfred LIEBERTHAL. "Plasmalogens as endogenous antioxidants: somatic cell mutants reveal the importance of the vinyl ether." Biochemical Journal 338, no. 3 (1999): 769–76. http://dx.doi.org/10.1042/bj3380769.

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Exposure of plasmalogen-deficient variants of the murine cell line RAW 264.7 to short-term (0–100 min) treatment with electron transport inhibitors antimycin A or cyanide (chemical hypoxia) resulted in a more rapid loss of viability than in the parent strain. Results suggested that plasmalogen-deficient cells were more sensitive to reactive oxygen species (ROS) generated during chemical hypoxia; the mutants could be rescued from chemical hypoxia by using the antioxidant Trolox, an α-tocopherol analogue, and they were more sensitive to ROS generation by plumbagin or by rose bengal treatment coupled with irradiation. In addition, the use of buffers containing 2H2O greatly enhanced the cytotoxic effect of chemical hypoxia, suggesting the involvement of singlet oxygen. We used the unique enzymic deficiencies displayed by the mutants to differentially restore either plasmenylethanolamine (the major plasmalogen species normally found in this cell line) or its biosynthetic precursor, plasmanylethanolamine. Restoration of plasmenylethanolamine, which contains the vinyl ether, resulted in wild-type-like resistance to chemical hypoxia and ROS generators, whereas increasing levels of its precursor, which bears the saturated ether, had no effect on cell survival. These findings identify the vinyl ether double bond as a crucial element in cellular protection under these conditions and support the hypothesis that plasmalogens, through the vinyl ether, act as antioxidants to protect cells against ROS. These phospholipids might protect cells from ROS-mediated damage during events such as chemical hypoxia.
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REISS, Daniela, Klaus BEYER, and Bernd ENGELMANN. "Delayed oxidative degradation of polyunsaturated diacyl phospholipids in the presence of plasmalogen phospholipids in vitro." Biochemical Journal 323, no. 3 (1997): 807–14. http://dx.doi.org/10.1042/bj3230807.

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The oxidative degradation of plasmalogen (alkenylacyl) phospholipids was analysed in the absence and the presence of polyunsaturated ester phospholipids by 1H-NMR and by chemical determination. Brain lysoplasmenylethanolamine (lyso-P-PE), brain P-PE and erythrocyte P-PE, containing an increasing number of intrachain double bonds at sn2, were oxidized with 2,2´-azobis-(2-amidinopropane hydrochloride) (AAPH; 2 or 10 mM) in Triton X-100 micelles (detergent/phospholipid 1:5, mol/mol). The formation of two peroxyl radicals was accompanied by the degradation of approx. one molecule of brain lyso-P-PE. On oxidation of brain P-PE or erythrocyte P-PE (320 nmol) with 2 mM AAPH, the (α-vinyl) methine 1H signal of the enol ether decreased more rapidly than the methine proton peak of intrachain double bonds. The rate of enol ether degradation increased in the order: erythrocyte P-PE > brain P-PE > brain lyso-P-PE. The disappearance of the polyunsaturated ester phospholipids 1-palmitoyl-2-arachidonoyl phosphatidylcholine (16:0/20:4-PC) and 1-palmitoyl-2-linoleoyl phosphatidylcholine (16:0/18:2-PC) (100 nmol), as induced by 10 mM AAPH, was nearly completely inhibited by the plasmalogens (25 nmol) in the first 30 and 60 min of incubation respectively, and was delayed at later time points. Plasmalogens and vitamin E (4–25 nmol) mitigated the decreases in 16:0/[3H]20:4-PC (100 nmol) induced by 2 mM AAPH in a similar manner. The initial rate of degradation of intrachain double bonds of 16:0/20:4-PC and 16:0/18:2-PC (320 nmol; 2 mM AAPH) was decreased by 59% and 81% respectively in the presence of 80 nmol of brain lyso-P-PE. In conclusion, plasmalogens markedly delay the oxidative degradation of intrachain double bonds under in vitro conditions. Interactions of enol ether double bonds with initiating peroxyl radicals as well as with products generated by prior oxidation of polyunsaturated fatty acids are proposed to be responsible for this capacity of plasmalogens. Furthermore, the products of enol ether oxidation apparently do not propagate the oxidation of polyunsaturated fatty acids.
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Krepinsky, Jiri J., Gabor P. Kandel, Ka Sing Yeung, et al. "From T-antigen to plasmalogen-derived aldehydes: The identification of a marker of colorectal cancer in human rectal mucous." Canadian Journal of Chemistry 81, no. 1 (2003): 109–17. http://dx.doi.org/10.1139/v02-195.

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Recently, a simple noninvasive screening test for colorectal cancer was proposed, based on a hypothesis involving galactose-containing carbohydrate moieties such as the Thomsen–Friedenreich antigen. According to the hypothesis, such carbohydrate moieties, present in the human rectal mucous of patients with colorectal cancer, can be specifically oxidized with galactose oxidase to form substances that, upon reaction with Schiff reagent, yield purple (magenta) coloured compounds. While evaluating this proposed test, we discovered that the colour formation is not due to the proposed reaction between oxidized galactose moieties present in rectal mucous and Schiff reagent. We found instead that the mucous from colorectal cancer patients contains compounds that form purple (magenta) adducts with the Schiff reagent directly, i.e., they do not require oxidation by galactose oxidase. We have identified these compounds as long-chain aliphatic aldehydes, mainly palmitic aldehyde C15H31CH=O and stearic aldehyde C17H35CH=O. We have further found that the aldehydes originate from plasmalogens present in the phospholipid fraction of the mucous obtained from colorectal cancer patients. The aldehydes, present in plasmalogens as enol ethers, are released by the acidity of the Schiff reagent and in turn react with the Schiff reagent to form the coloured adducts. Correct identification of these markers could lead to the development of a more accurate colorectal cancer screening tool and to a deeper understanding of colorectal carcinogenesis.Key words: T-antigen, plasmalogen-derived aldehydes, colorectal cancer marker.
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Yamashita, Shinji, Susumu Kanno, Kiyotaka Nakagawa, Mikio Kinoshita, and Teruo Miyazawa. "Extrinsic plasmalogens suppress neuronal apoptosis in mouse neuroblastoma Neuro-2A cells: importance of plasmalogen molecular species." RSC Advances 5, no. 75 (2015): 61012–20. http://dx.doi.org/10.1039/c5ra00632e.

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Plasmalogen, especially those having 22:6, suppressed neuronal apoptosisviadeath receptor and mitochondrial pathways. These mechanisms of action of plasmalogen may be responsible for regulation of membrane functions and second messenger production.
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Prasch, Jürgen, Eva Bernhart, Helga Reicher, et al. "Myeloperoxidase-Derived 2-Chlorohexadecanal Is Generated in Mouse Heart during Endotoxemia and Induces Modification of Distinct Cardiomyocyte Protein Subsets In Vitro." International Journal of Molecular Sciences 21, no. 23 (2020): 9235. http://dx.doi.org/10.3390/ijms21239235.

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Sepsis is a major cause of mortality in critically ill patients and associated with cardiac dysfunction, a complication linked to immunological and metabolic aberrations. Cardiac neutrophil infiltration and subsequent release of myeloperoxidase (MPO) leads to the formation of the oxidant hypochlorous acid (HOCl) that is able to chemically modify plasmalogens (ether-phospholipids) abundantly present in the heart. This reaction gives rise to the formation of reactive lipid species including aldehydes and chlorinated fatty acids. During the present study, we tested whether endotoxemia increases MPO-dependent lipid oxidation/modification in the mouse heart. In hearts of lipopolysaccharide-injected mice, we observed significantly higher infiltration of MPO-positive cells, increased fatty acid content, and formation of 2-chlorohexadecanal (2-ClHDA), an MPO-derived plasmalogen modification product. Using murine HL-1 cardiomyocytes as in vitro model, we show that exogenously added HOCl attacks the cellular plasmalogen pool and gives rise to the formation of 2-ClHDA. Addition of 2-ClHDA to HL-1 cardiomyocytes resulted in conversion to 2-chlorohexadecanoic acid and 2-chlorohexadecanol, indicating fatty aldehyde dehydrogenase-mediated redox metabolism. However, a recovery of only 40% indicated the formation of non-extractable (protein) adducts. To identify protein targets, we used a clickable alkynyl analog, 2-chlorohexadec-15-yn-1-al (2-ClHDyA). After Huisgen 1,3-dipolar cycloaddition of 5-tetramethylrhodamine azide (N3-TAMRA) and two dimensional-gel electrophoresis (2D-GE), we were able to identify 51 proteins that form adducts with 2-ClHDyA. Gene ontology enrichment analyses revealed an overrepresentation of heat shock and chaperone, energy metabolism, and cytoskeletal proteins as major targets. Our observations in a murine endotoxemia model demonstrate formation of HOCl-modified lipids in the heart, while pathway analysis in vitro revealed that the chlorinated aldehyde targets specific protein subsets, which are central to cardiac function.
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27

Abe, Yuichi, Masanori Honsho, Ryoko Kawaguchi, et al. "A peroxisome deficiency–induced reductive cytosol state up-regulates the brain-derived neurotrophic factor pathway." Journal of Biological Chemistry 295, no. 16 (2020): 5321–34. http://dx.doi.org/10.1074/jbc.ra119.011989.

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The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function.
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Hara, Hiroshi, Takuya Wakisaka, and Yoritaka Aoyama. "Lymphatic absorption of plasmalogen in rats." British Journal of Nutrition 90, no. 1 (2003): 29–32. http://dx.doi.org/10.1079/bjn2003879.

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Plasmalogen is a subclass of phospholipids that is widely distributed in man and animals. Many physiological roles have been proposed for this lipid; however, there have been no reports on the intestinal absorption of plasmalogen. In the present study, we examined lymphatic absorption of plasmalogen after the duodenal infusion of emulsified brain phospholipids (BPL) containing plasmalogen (22 mol% of total phospholipids) and soyabean lecithin (SPL) (100 g emulsified phospholipid/l). Male Wistar rats with implanted cannulas in the mesenteric lymph duct and the duodenum were kept in a Bollman-type restraining cage, and were infused the emulsion after 1 d recovery with duodenal infusion of a glucose–NaCl solution. Lymphatic plasmalogen output was increased at 2–4 h after the switch to BPL emulsion, and peaked at 4–6 h. However, no increases were observed after SPL infusion. Lymphatic recovery of plasmalogen for 8 h was 198 nmol, which was 0·22 mol% of the total plasmalogen disappeared from the intestine. We did not detect any increases in long-chain fatty aldehydes, which are the degradation product of plasmalogen, either in the blood or the small intestine. We conclude that a small percentage but a significant amount of the plasmalogen was absorbed into the lymph.
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29

Gostry, A. V., A. V. Simonova, N. A. Mikhailova, et al. "CHRONIC PHARYNGITIS: ETIOLOGY, PATHOGENESIS, TREATMENT. NEW APPROACHES TO THE ESTIMATION OF ETIOPATOGENESIS." Russian Archives of Internal Medicine 9, no. 1 (2019): 32–43. http://dx.doi.org/10.20514/2226-6704-2019-9-1-32-43.

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The work discusses modern issues of etiopathogenesis, treatment of chronic pharyngitis. The results of the application of a modern method for the diagnosis of mass spectrometry of microbial markers (MSMM), which allows to detect the microorganisms in a biofilm, in a “sleeping state” under the protection of mucin are presented. With the help of this express method, it is possible to conduct a determination of the content in a smear from the pharynx 57 biomarkers of microorganisms at the same time 2 hours after delivery to the laboratory. It was found that 100% of the examined patients with a recurring course of HF (n = 62) increased the total content of microorganisms, which indicates the need for antibacterial therapy; 87% of patients have elevated levels of endotoxin, which is a sign of general intoxication; 71% of patients have reduced plasmalogene content and these patients may be at increased risk for lipid metabolic disturbances; in 100% of the examined patients with frequent exacerbations of CP in the pharynx the nasopharyngeal microflora (coccal) is determined, as well as new etiopathogenetically significant microorganisms (not detected by PCR and cultures), among which there are 7 transient microorganisms (normally in the orifice their level = 0), 11 resident (6- found in the throat in the norm in the minimum level and 5 in the high content). Also, with the help of MSMM, a significant or moderate increase in the content of herpes, cytomegalovirus was detected in the majority (75%) of patients, which indicates the important role of the viruses of the herpes group in the etiopathogenesis in the recurrent course of CP; level of Candida spp. elevated in half of patients; the content of normal microflora is increased in 71% of patients, which indicates the preservation of local resistance in patients with chronic HF, examined by the authors. Thus, the use of MSMM for chronic fever allows to identify new etiopathogenetic microorganisms, on this basis to prescribe a more effective therapy. Thus? it is possible to carry out personified, more effective treatment.
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30

Kimura, Tomohiro, Atsuko K. Kimura, Mindong Ren, et al. "Plasmalogen loss caused by remodeling deficiency in mitochondria." Life Science Alliance 2, no. 4 (2019): e201900348. http://dx.doi.org/10.26508/lsa.201900348.

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Lipid homeostasis is crucial in human health. Barth syndrome (BTHS), a life-threatening disease typically diagnosed with cardiomyopathy and neutropenia, is caused by mutations in the mitochondrial transacylase tafazzin. By high-resolution 31P nuclear magnetic resonance (NMR) with cryoprobe technology, recently we found a dramatic loss of choline plasmalogen in the tafazzin-knockdown (TAZ-KD) mouse heart, besides observing characteristic cardiolipin (CL) alterations in BTHS. In inner mitochondrial membrane where tafazzin locates, CL and diacyl phosphatidylethanolamine are known to be essential via lipid–protein interactions reflecting their cone shape for integrity of respiratory chain supercomplexes and cristae ultrastructure. Here, we investigate the TAZ-KD brain, liver, kidney, and lymphoblast from patients compared with controls. We identified common yet markedly cell type–dependent losses of ethanolamine plasmalogen as the dominant plasmalogen class therein. Tafazzin function thus critically relates to homeostasis of plasmalogen, which in the ethanolamine class has conceivably analogous and more potent molecular functions in mitochondria than diacyl phosphatidylethanolamine. The present discussion of a loss of plasmalogen–protein interaction applies to other diseases with mitochondrial plasmalogen loss and aberrant forms of this organelle, including Alzheimer's disease.
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31

Flasiński, Michał, Katarzyna Hąc-Wydro, Paweł Wydro, and Patrycja Dynarowicz-Łątka. "Influence of platelet-activating factor, lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level." Journal of The Royal Society Interface 11, no. 95 (2014): 20131103. http://dx.doi.org/10.1098/rsif.2013.1103.

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Three structurally related but differing in biological activities single-chained ether phospholipids (PAF (platelet-activating factor) and lyso-PAF) and an anti-cancer drug (edelfosine (ED)) were investigated in Langmuir monolayers imitating natural membranes. The aim of the undertaken experiments was to study the influence of these lipids on monolayers mimicking plasma membranes of cell lines differing in susceptibility to the anti-cancer activity of ED, i.e. promyelocytic leukaemia cells (HL-60) and promyeloblastic leukaemia cells (K-562). As these cells differ essentially in the cholesterol/phospholipid ratio and plasmalogen concentration in the membrane, we have carried out systematic investigations in artificial systems of various compositions. The results for model leukaemia cell membrane were compared with data acquired for systems imitating normal leucocytes. Our results show that the level of plasmalogens significantly modulates the influence of the single-chained phospholipids on the investigated systems. The experiments confirmed also that the interactions of ether lipids with a model membrane of HL-60 cells (in biological tests sensitive to ED) have opposite character when compared with K-562, being resistant to ED. Moreover, the values of the parameters characterizing monolayers serving as membrane models (strength of interactions, monolayers fluidity and morphology) proved both sensitivity of these cells to ED and lack of their susceptibility towards PAF. Interestingly, it has been found that lyso-PAF, which is usually described as an inactive precursor of PAF, displays a stronger effect on HL-60 model membranes than ED.
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32

Takahashi, Takumi, Reina Kamiyoshihara, Yurika Otoki, et al. "Structural changes of ethanolamine plasmalogen during intestinal absorption." Food & Function 11, no. 9 (2020): 8068–76. http://dx.doi.org/10.1039/d0fo01666g.

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A part of ethanolamine plasmalogen (PE-Pls) undergoes structural changes (i.e., arachidonic acid re-esterification and base conversion of PE-Pls into choline plasmalogen (PC-Pls)) during intestinal absorption.
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33

Leßig, J., and B. Fuchs. "Plasmalogens in Biological Systems: Their Role in Oxidative Processes in Biological Membranes, their Contribution to Pathological Processes and Aging and Plasmalogen Analysis." Current Medicinal Chemistry 16, no. 16 (2009): 2021–41. http://dx.doi.org/10.2174/092986709788682164.

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34

Oberg, Taylor S., Robert E. Ward, James L. Steele, and Jeff R. Broadbent. "Identification of Plasmalogens in the Cytoplasmic Membrane of Bifidobacterium animalis subsp. lactis." Applied and Environmental Microbiology 78, no. 3 (2011): 880–84. http://dx.doi.org/10.1128/aem.06968-11.

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ABSTRACTPlasmalogens are ether-linked lipids that may influence oxidative stress resistance of eukaryotic cell membranes. Since bacterial membrane composition can influence environmental stress resistance, we explored the prevalence of plasmalogens in the cytoplasmic membrane ofBifidobacterium animalissubsp.lactis. Results showed plasmalogens are a major component of theB. animalissubsp.lactismembrane.
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35

Wood, Paul L., Brooke L. Barnette, Jeffrey A. Kaye, Joseph F. Quinn, and Randall L. Woltjer. "Non-targeted lipidomics of CSF and frontal cortex grey and white matter in control, mild cognitive impairment, and Alzheimer’s disease subjects." Acta Neuropsychiatrica 27, no. 5 (2015): 270–78. http://dx.doi.org/10.1017/neu.2015.18.

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ObjectiveWe undertook a non-targeted lipidomics analysis of post-mortem cerebrospinal fluid (CSF), frontal cortex grey matter, and subjacent white matter to define potential biomarkers that distinguish cognitively intact subjects from those with incipient or established dementia. Our objective was to increase our understanding of the role of brain lipids in pathophysiology of aging and age-related cognitive impairment.MethodsLevels of 650 individual lipids, across 26 lipid subclasses, were measured utilising a high-resolution mass spectrometric analysis platform.ResultsMonoacylglycerols (MAG), diacylglycerols (DAG), and the very-long-chain fatty acid 26:0 were elevated in the grey matter of the mild cognitive impairment (MCI) and old dementia (OD) cohorts. Ethanolamine plasmalogens (PlsEtn) were decreased in the grey matter of the young dementia (YD) and OD cohorts while and phosphatidylethanolamines (PtdEth) were lower in the MCI, YD and OD cohorts. In the white matter, decrements in sulphatide levels were detected in the YD group, DAG levels were elevated in the MCI group, and MAG levels were increased in the YD and OD groups.ConclusionThe parallel changes in grey matter MAGs and DAGs in the MCI and OD groups suggest that these two cohorts may have a similar underlying pathophysiology; consistent with this, MCI subjects were more similar in age to OD than to YD subjects. While PlsEtn and phosphatidylethanolamine were decreased in the YD and OD groups they were unaltered in the MCI group indicating that alterations in plasmalogen synthesis are unlikely to represent an initiating event in the transition from MCI to dementia.
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36

Mawatari, Shiro, Shinji Ohara, Yoshihide Taniwaki, Yoshio Tsuboi, Toru Maruyama, and Takehiko Fujino. "Improvement of Blood Plasmalogens and Clinical Symptoms in Parkinson’s Disease by Oral Administration of Ether Phospholipids: A Preliminary Report." Parkinson's Disease 2020 (February 19, 2020): 1–7. http://dx.doi.org/10.1155/2020/2671070.

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Introduction. Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD). With the ageing of population, the frequency of PD is expected to increase dramatically in the coming decades. L-DOPA (1,3,4-dihydroxyalanine) is the most effective drug in the symptomatic treatment of PD. Nonmotor symptoms in PD include sleep problems, depression, and dementia, which are not adequately controlled with dopaminergic therapy. Here, we report the efficacy of oral administration of scallop-derived ether phospholipids to some nonmotor symptoms of PD. Methods. Ten (10) patients received oral administration of 1 mg/day of purified ether phospholipids derived from scallop for 24 weeks. Clinical symptoms and blood tests were checked at 0, 4, 12, 24, and 28 weeks. The blood levels of plasmalogens in patients with PD were compared with those of 39 age-matched normal controls. Results. Initial levels of plasma ethanolamine ether phospholipids in PD and ethanolamine plasmalogen of erythrocyte from PD were lower than those of age-matched normal controls. Oral administration of 1 mg/day of the purified ether phospholipids increased plasma ether phospholipids in PD and increased the relative composition of ether phospholipids of erythrocyte membrane in PD. The levels of ether phospholipids in peripheral blood reached to almost normal levels after 24 weeks. Furthermore, some clinical symptoms of PD improved concomitantly. Conclusion. 1 mg/day of oral administration of purified ether phospholipids derived from scallop can increase ether phospholipids in peripheral blood and concomitantly improve some clinical symptoms of PD.
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Takahashi, Takanori, Masanori Honsho, Yuichi Abe, and Yukio Fujiki. "Plasmalogen mediates integration of adherens junction." Journal of Biochemistry 166, no. 5 (2019): 423–32. http://dx.doi.org/10.1093/jb/mvz049.

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AbstractEther glycerolipids, plasmalogens are found in various mammalian cells and tissues. However, physiological role of plasmalogens in epithelial cells remains unknown. We herein show that synthesis of ethanolamine-containing plasmalogens, plasmenylethanolamine (PlsEtn), is deficient in MCF7 cells, an epithelial cell line, with severely reduced expression of alkyl-dihydroxyacetonephosphate synthase (ADAPS), the second enzyme in the PlsEtn biosynthesis. Moreover, expression of ADAPS or supplementation of PlsEtn containing C18-alkenyl residue delays the migration of MCF7 cells as compared to that mock-treated MCF7 and C16-alkenyl-PlsEtn-supplemented MCF7 cells. Localization of E-cadherin to cell–cell junctions is highly augmented in cells containing C18-alkenyl-PlsEtn. Together, these results suggest that PlsEtn containing C18-alkenyl residue plays a distinct role in the integrity of E-cadherin-mediated adherens junction.
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38

Nagan, Narasimhan, and Raphael A. Zoeller. "Plasmalogens: biosynthesis and functions." Progress in Lipid Research 40, no. 3 (2001): 199–229. http://dx.doi.org/10.1016/s0163-7827(01)00003-0.

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39

MAEBA, Ryouta. "Antioxidative Effect of Plasmalogens." Oleoscience 2, no. 1 (2002): 27–36. http://dx.doi.org/10.5650/oleoscience.2.27.

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40

YAMAGUCHI, TOSHIYASU, SHIGEO YAGI, TOSHIKI NAKANO, MASAAKI TAKEUCHI, and MINORU SATO. "Plasmalogen of fish lipoprotein." Fisheries science 68, sup2 (2002): 1202–5. http://dx.doi.org/10.2331/fishsci.68.sup2_1202.

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41

Goldfine, Howard. "Cytochromectakes on plasmalogen catabolism." Journal of Biological Chemistry 293, no. 22 (2018): 8710–11. http://dx.doi.org/10.1074/jbc.h118.003072.

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42

NISHIMUKAI, Megumi, Ryouta MAEBA, and Hiroshi HARA. "Analytical Methods for Plasmalogen." Oleoscience 21, no. 8 (2021): 321–28. http://dx.doi.org/10.5650/oleoscience.21.321.

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43

Honsho, Masanori, and Yukio Fujiki. "Plasmalogen homeostasis – regulation of plasmalogen biosynthesis and its physiological consequence in mammals." FEBS Letters 591, no. 18 (2017): 2720–29. http://dx.doi.org/10.1002/1873-3468.12743.

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44

Nishimukai, Megumi, Takuya Wakisaka, and Hiroshi Hara. "Ingestion of plasmalogen markedly increased plasmalogen levels of blood plasma in rats." Lipids 38, no. 12 (2003): 1227–35. http://dx.doi.org/10.1007/s11745-003-1183-9.

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45

Bezrodny, S. L., S. G. Mardanly, A. M. Zatevalov, E. V. Tereshina, A. Yu Mironov, and V. V. Pomazanov. "Assessment of the state of intestinal microbiocenosis based on bacterial endotoxin and plasmalogen in elderly persons with type 2 diabetes mellitus pathology." Russian Clinical Laboratory Diagnostics 66, no. 9 (2021): 565–70. http://dx.doi.org/10.51620/0869-2084-2021-66-9-565-570.

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The concentration of bacterial plasmalogen 18a and endotoxin in the blood of elderly people 45-90 years old with the pathology of type 2 diabetes mellitus (DM 2) - the main group and without diabetes mellitus - the comparison group was investigated. The concentration of both plasmalogen 18a and endotoxin in the blood of individuals with DM 2 pathology is statistically significantly higher than in the blood of individuals without DM 2 pathology. To assess the state of microbiocenosis and predict type 2 diabetes mellitus, decisive rules have been determined in the form of threshold values of plasma concentrations 18a and endotoxin in the blood of elderly people with a suspected or established diagnosis of type 2 diabetes. Using ROC analysis, it was found that values above 20.66 μg / ml for plasmalogen 18a, and 0.48 nmol / ml for endotoxin, determine the presence of type 2 diabetes mellitus pathology in the 45-90 age group.
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46

Malik, Vasanti S., Marta Guasch-Ferre, Frank B. Hu, et al. "Identification of Plasma Lipid Metabolites Associated with Nut Consumption in US Men and Women." Journal of Nutrition 149, no. 7 (2019): 1215–21. http://dx.doi.org/10.1093/jn/nxz048.

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ABSTRACT Background Intake of nuts has been inversely associated with risk of type 2 diabetes and cardiovascular disease, partly through inducing a healthy lipid profile. How nut intake may affect lipid metabolites remains unclear. Objective The aim of this study was to identify the plasma lipid metabolites associated with habitual nut consumption in US men and women. Methods We analyzed cross-sectional data from 1099 participants in the Nurses’ Health Study (NHS), NHS II, and Health Professionals Follow-up Study. Metabolic profiling was conducted on plasma by LC–mass spectrometry. Nut intake was estimated from food-frequency questionnaires. We included 144 known lipid metabolites that had CVs ≤25%. Multivariate linear regression was used to assess the associations of nut consumption with individual plasma lipid metabolites. Results We identified 17 lipid metabolites that were significantly associated with nut intake, based on a 1 serving (28 g)/d increment in multivariate models [false discovery rate (FDR) P value <0.05]. Among these species, 8 were positively associated with nut intake [C24:0 sphingomyelin (SM), C36:3 phosphatidylcholine (PC) plasmalogen-A, C36:2 PC plasmalogen, C24:0 ceramide, C36:1 PC plasmalogen, C22:0 SM, C34:1 PC plasmalogen, and C36:2 phosphatidylethanolamine plasmalogen], with changes in relative metabolite level (expressed in number of SDs on the log scale) ranging from 0.36 to 0.46 for 1 serving/d of nuts. The other 9 metabolites were inversely associated with nut intake with changes in relative metabolite level ranging from −0.34 to −0.44. In stratified analysis, 3 metabolites were positively associated with both peanuts and peanut butter (C24:0 SM, C24:0 ceramide, and C22:0 SM), whereas 6 metabolites were inversely associated with other nuts (FDR P value <0.05). Conclusions A panel of lipid metabolites was associated with intake of nuts, which may provide insight into biological mechanisms underlying associations between nuts and cardiometabolic health. Metabolites that were positively associated with intake of nuts may be helpful in identifying potential biomarkers of nut intake.
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NISHIMUKAI, Megumi, Hiroshi HARA, and Ryouta MAEBA. "Absorptive Characteristics of Plasmalogen and Availability of Serum/Plasma Plasmalogen as the Biomarker." Oleoscience 15, no. 2 (2015): 53–60. http://dx.doi.org/10.5650/oleoscience.15.53.

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Loidl, Josef, Georg Schwabe, Eduard Paschke, Fritz Paltauf, and Albin Hermetter. "Uptake of fluorescent plasmalogen analogs by cultured human skin fibroblasts deficient in plasmalogen." Biochimica et Biophysica Acta (BBA) - Biomembranes 1029, no. 1 (1990): 75–84. http://dx.doi.org/10.1016/0005-2736(90)90438-t.

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49

Ding, Ming, Oana A. Zeleznik, Marta Guasch-Ferre, et al. "Metabolome-Wide Association Study of the Relationship Between Habitual Physical Activity and Plasma Metabolite Levels." American Journal of Epidemiology 188, no. 11 (2019): 1932–43. http://dx.doi.org/10.1093/aje/kwz171.

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Abstract We identified plasma metabolites associated with habitual physical activity among 5,197 US participants from the Nurses’ Health Study (NHS), Nurses’ Health Study II (NHS II), and the Health Professionals Follow-up Study (HPFS). Physical activity was assessed every 2–4 years via self-report questionnaires. Blood was collected in the NHS in 1989–1990, in NHS II during 1996–1999, and in the HPFS during 1993–1995. Metabolic profiling was conducted by liquid chromatography–mass spectrometry. Our study included 337 known metabolites, with 256 of them classified as lipids. We corrected for multiple testing by controlling the tail probability of the proportion of false positives (TPPFP) and accounted for correlated tests using bootstrapping. Physical activity was significantly associated with 20 metabolites after correction for multiple testing (TPPFP < 0.05), and positive associations were found for most of the metabolites, including 2 amino acids (citrulline and glycine), 4 cholesteryl esters (C18:2, C18:1, C16:0, C18:3), 8 phosphocholines (PCs) (C36:4 PC-A, C34:3 PC plasmalogen, C36:3 PC plasmalogen, C34:2 PC plasmalogen, C36:2 PC) and lysophosphatidylcholines (C18:2, C20:5, C18:1), and 3 phosphatidylethanolamines (PEs) (C38:3 PE plasmalogen) and lysophosphatidylethanolamines (C18:2, C18:1). We independently replicated the 20 metabolites among 2,305 women in the Women’s Health Initiative using 1993 data, and half of the metabolites were replicated. Our study may help identify biomarkers of physical activity and provide insight into biological mechanisms underlying the beneficial effect of being physically active on cardiometabolic health.
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Goldfine, Howard. "The anaerobic biosynthesis of plasmalogens." FEBS Letters 591, no. 18 (2017): 2714–19. http://dx.doi.org/10.1002/1873-3468.12714.

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