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Biochimica Et Biophysica Acta Dec 2006Chemical and physico-chemical properties as well as physiological functions of major mammalian ether-linked glycerolipids, including plasmalogens were reviewed. Their... (Review)
Review
Chemical and physico-chemical properties as well as physiological functions of major mammalian ether-linked glycerolipids, including plasmalogens were reviewed. Their chemical structures were described and their effect on membrane fluidity and membrane fusion discussed. The recent generation of mouse models with ether lipid deficiency offered the possibility to study ether lipid and particularly plasmalogen functions in vivo. Ether lipid-deficient mice revealed severe phenotypic alterations, including arrest of spermatogenesis, development of cataract and defects in central nervous system myelination. In several cell culture systems lack of plasmalogens impaired intracellular cholesterol distribution affecting plasma membrane functions and structural changes of ER and Golgi cisternae. Based on these phenotypic anomalies that were accurately described conclusions were drawn on putative functions of plasmalogens. These functions were related to cell-cell or cell-extracellular matrix interactions, formation of lipid raft microdomains and intracellular cholesterol homeostasis. There are several human disorders, such as Zellweger syndrome, rhizomelic chondrodysplasia punctata, Alzheimer's disease, Down syndrome, and Niemann-Pick type C disease that are distinguished by altered tissue plasmalogen concentrations. The role plasmalogens might play in the pathology of these disorders is discussed.
Topics: Acyltransferases; Animals; Cataract; Cell Membrane; Cholesterol; Endoplasmic Reticulum; Golgi Apparatus; Hereditary Central Nervous System Demyelinating Diseases; Lens, Crystalline; Male; Membrane Fluidity; Membrane Fusion; Mice; Mice, Knockout; Peroxisomal Targeting Signal 2 Receptor; Plasmalogens; Receptors, Cytoplasmic and Nuclear; Spermatogenesis
PubMed: 17027098
DOI: 10.1016/j.bbamcr.2006.08.038 -
The Journal of Biological Chemistry Nov 2015Plasmalogen biosynthesis is regulated by modulating fatty acyl-CoA reductase 1 stability in a manner dependent on cellular plasmalogen level. However, physiological...
Plasmalogen biosynthesis is regulated by modulating fatty acyl-CoA reductase 1 stability in a manner dependent on cellular plasmalogen level. However, physiological significance of the regulation of plasmalogen biosynthesis remains unknown. Here we show that elevation of the cellular plasmalogen level reduces cholesterol biosynthesis without affecting the isoprenylation of proteins such as Rab and Pex19p. Analysis of intermediate metabolites in cholesterol biosynthesis suggests that the first oxidative step in cholesterol biosynthesis catalyzed by squalene monooxygenase (SQLE), an important regulator downstream HMG-CoA reductase in cholesterol synthesis, is reduced by degradation of SQLE upon elevation of cellular plasmalogen level. By contrast, the defect of plasmalogen synthesis causes elevation of SQLE expression, resulting in the reduction of 2,3-epoxysqualene required for cholesterol synthesis, hence implying a novel physiological consequence of the regulation of plasmalogen biosynthesis.
Topics: Animals; CHO Cells; Cholesterol; Cricetinae; Cricetulus; Gene Expression Regulation, Enzymologic; HEK293 Cells; HeLa Cells; Homeostasis; Humans; Hydroxymethylglutaryl CoA Reductases; Membrane Proteins; Plasmalogens; Protein Prenylation; Squalene Monooxygenase; rab GTP-Binding Proteins
PubMed: 26463208
DOI: 10.1074/jbc.M115.656983 -
Brain Research Sep 2021Scallop-derived plasmalogen (sPlas) has both anti-oxidative and anti-inflammation activities, but its efficacy has not been investigated in ischemic stroke models where...
Scallop-derived plasmalogen (sPlas) has both anti-oxidative and anti-inflammation activities, but its efficacy has not been investigated in ischemic stroke models where oxidative stress, inflammation, and neurovascular unit (NVU) damage accelerates pathophysiological progression. Therefore, in the present study, we aimed to assess the neuroprotective effects of sPlas in ischemic stroke by using a transient middle cerebral artery occlusion (tMCAO) mouse model. After the pretreatment of vehicle or sPlas (10 mg/kg/day) for 14 days, adult male mice were subjected to tMCAO for 60 min, then continuously treated with vehicle or sPlas during reperfusion and for an additional 5 days. The administration of sPlas significantly improved motor deficits (corner and rotarod tests, *p < 0.05 vs vehicle), enhanced serum antioxidative activity (OXY-adsorbent and d-ROMs tests, *p < 0.05 vs vehicle), reduced infarction volume (*p < 0.05 vs vehicle), decreased the expression of two oxidative stress markers, 4-HNE (*p < 0.05 vs vehicle) and 8-OHdG (*p < 0.05 vs vehicle), decreased the expression of pro-inflammatory markers Iba-1 (**p < 0.01 vs vehicle), IL-1β (**p < 0.01 vs vehicle), and TNF-α (**p < 0.01 vs vehicle), and alleviated NVU damage (collagen IV, MMP9, and GFAP/collagen IV, *p < 0.05 vs vehicle). Our present findings are the first to demonstrate the neuroprotective effects of sPlas on acute ischemic stroke mice at 5 d after tMCAO via anti-oxidative stress, anti-inflammation, and improvement of NVU damage, suggesting the potential of sPlas in preventing and treating ischemic stroke.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Brain Ischemia; Ischemic Stroke; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Oxidative Stress; Pectinidae; Plasmalogens; Treatment Outcome
PubMed: 33991494
DOI: 10.1016/j.brainres.2021.147516 -
Brain Research Nov 2017Ethanolamine plasmalogens (PlsEtn) are a class of glycerophospholipids characterized by a vinyl-ether bond at the sn-1 position that play an important role in the...
Ethanolamine plasmalogens (PlsEtn) are a class of glycerophospholipids characterized by a vinyl-ether bond at the sn-1 position that play an important role in the structure and function of membranes. Previous reports have suggested a link between reduced blood and brain PlsEtn levels and Parkinson's disease (PD). We recently reported that the DHA containing plasmalogen precursor PPI-1011 protected striatal dopamine (DA) against MPTP toxicity in mice. In this paper, we further investigate the specificity requirements of the lipid side chains by testing the oleic acid-containing plasmalogen precursor PPI-1025. Male mice were treated for 10days with daily oral administration of PPI-1025 (10, 50 or 200mg/kg). On day 5 mice received MPTP and were sacrificed on Day 11. Treatment with PPI-1025 prevented MPTP-induced decrease of DA and serotonin, as well as their metabolites. In addition, PPI-1025 treatment prevented the MPTP-induced decrease of the striatal dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) specific binding. Significant positive correlations were measured between striatal DA concentrations and DAT or VMAT2 specific binding, as well as with serum plasmalogen concentrations. The neuroprotective effect of PPI-1025 displayed a bell-curve dose-dependency losing effect at the highest dose tested. The similar protective response of oleic and docosahexaenoic acid (DHA)-containing plasmalogen precursors suggests that the neuroprotection observed is not only due to DHA but to the oleic substituent and the plasmalogen backbone.
Topics: Animals; Biomarkers, Pharmacological; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Male; Mice; Mice, Inbred C57BL; Neostriatum; Neuroprotective Agents; Parkinson Disease; Plasmalogens; Serotonin; Vesicular Monoamine Transport Proteins
PubMed: 28830769
DOI: 10.1016/j.brainres.2017.08.020 -
Journal of Oleo Science Feb 2021Ethanolamine plasmalogen (PlsEtn), a subclass of ethanolamine glycerophospholipid (EtnGpl), has been reported to have many biological and dietary functions. In terms of...
Ethanolamine plasmalogen (PlsEtn), a subclass of ethanolamine glycerophospholipid (EtnGpl), has been reported to have many biological and dietary functions. In terms of PlsEtn absorption, some studies have reported that PlsEtn is re-esterized at the sn-2 position using lymph cannulation and the everted jejunal sac model. In this study, we aimed to better understand the uptake kinetics of PlsEtn and increase its absorption. We thus compared the uptake kinetics of PlsEtn with that of the lyso-form, in which the fatty acid at the sn-2 position was hydrolyzed enzymatically. Upon administration of EtnGpl (extracted from oysters or ascidians, 75.4 mol% and 88.4 mol% of PlsEtn ratio, respectively), the plasma PlsEtn species in mice showed the highest levels at 4 or 8 hours after administration. In the contrast, administration of the EtnGpl hydrolysate, which contained lysoEtnGpl and free fatty acids, markedly increased the plasma levels of PlsEtn species at 2 h after administration. The area under the plasma concentration-time curve (AUC), especially the AUC of PlsEtn species, was higher with hydrolysate administration than that with EtnGpl administration. These results indicate that EtnGpl hydrolysis accelerated the absorption and metabolism of PlsEtn. Consequently, using a different experimental approach from that used in previous studies, we reconfirmed that PlsEtn species were absorbed via hydrolysis at the sn-2 position, suggesting that hydrolysis in advance could increase PlsEtn uptake.
Topics: Administration, Oral; Animals; Intestinal Absorption; Male; Mice, Inbred ICR; Ostreidae; Plasmalogens; Protein Hydrolysates; Mice
PubMed: 33456005
DOI: 10.5650/jos.ess20223 -
Advances in Experimental Medicine and... 1996Plasmalogens are hydrolyzed by a plasmalogen-selective phospholipase A2. This enzyme, purified from bovine brain, does not require Ca2+ and is localized in cytosol. It... (Review)
Review
Plasmalogens are hydrolyzed by a plasmalogen-selective phospholipase A2. This enzyme, purified from bovine brain, does not require Ca2+ and is localized in cytosol. It has a molecular mass of 39 kDa and is strongly inhibited by glycosaminoglycans, gangliosides, and sialoglycoproteins. These molecules may be involved in the regulation of its enzymic activity. Plasmalogen-selective phospholipase A2 plays an important role in the release of free fatty acids and platelet-activating factor during trauma.
Topics: Animals; Brain; Brain Chemistry; Cattle; Humans; Phospholipases A; Phospholipases A2; Plasmalogens; Platelet Activating Factor
PubMed: 9131165
DOI: 10.1007/978-1-4899-0179-8_49 -
Biochimica Et Biophysica Acta.... Sep 2023Plasmalogens (Pls) are vinyl-ether bond-containing glycerophospholipids or glycosyl diradyl glycerols, and are of great importance in the physiological functions and...
Plasmalogens (Pls) are vinyl-ether bond-containing glycerophospholipids or glycosyl diradyl glycerols, and are of great importance in the physiological functions and stability of cell membrane. Here, we identified and characterized that the plasmalogen synthase MeHAD from anaerobic Megasphaera elsdenii was responsible for vinyl-ether bond formation. Different from the 2-hydroxyacyl-CoA dehydratase (HAD) family plasmalogen synthase PlsA-PlsR which are encoded by two genes in Clostridium perfringens, the HAD homolog (MeHAD) encoded by a single gene MELS_0169 was found in M. elsdenii. By heterologous expression of the MeHAD gene into a nonplasmalogen-producing Escherichia coli strain, the expressed MeHAD was found to be located in the cell membrane region. Plasmalogens were detected in the recombinant strain using GC-MS and LC-MS, demonstrating that MeHAD was the key enzyme for plasmalogen synthesis. Moreover, the synthesized plasmalogens could enhance the oxidative stress-resistance and osmotic pressure-resistance of the recombinant strain, probably due to the ROS scavenging and decreased membrane permeability by the plasmalogens, respectively. The four-cysteine (Cys125, Cys164, Cys445 and Cys484) site-mutant of MeHAD, which were predicted binding to the [4Fe-4S] cluster, was unable to synthesize plasmalogens, indicating that the cysteines are important for the catalytic activity of MeHAD. Our results revealed the single gene encoded plasmalogen synthase in M. elsdenii and established a recombinant E. coli strain with plasmalogen production potential.
Topics: Plasmalogens; Megasphaera elsdenii; Escherichia coli; Ethers
PubMed: 37348645
DOI: 10.1016/j.bbalip.2023.159358 -
Methods in Molecular Biology (Clifton,... 2017Plasmalogen synthesis can be analyzed by metabolic labeling, followed by the separation of ethanolamine plasmalogens from glycerophospholipids on one-dimensional...
Plasmalogen synthesis can be analyzed by metabolic labeling, followed by the separation of ethanolamine plasmalogens from glycerophospholipids on one-dimensional thin-layer chromatography. The vinyl-ether bond of plasmalogens is acid-labile, which allows separating plasmalogens as 2-acyl-glycerophospholipids from diacyl-glycerophospholipids.
Topics: Carbon Radioisotopes; Cell Line; Cells, Cultured; Ethanolamine; Isotope Labeling; Palmitic Acid; Plasmalogens; Vinyl Compounds
PubMed: 28409451
DOI: 10.1007/978-1-4939-6937-1_6 -
Biochemical and Biophysical Research... Jun 2022Plasmalogen localized in the raft of mammalian cell membranes plays a role in the storage of polyunsaturated fatty acid (PUFA), and exists to a higher extent in...
Plasmalogen localized in the raft of mammalian cell membranes plays a role in the storage of polyunsaturated fatty acid (PUFA), and exists to a higher extent in malignant cells that survive, and even grow in hypoxic conditions. The biosynthesis of plasmalogen in mammalian cells has been reported to depend on aerobic conditions. Using liquid chromatography-tandem mass spectrometry, we found that the intracellular concentration of plasmalogen species containing a PUFA at the sn-2-position did not change for two days from the start of hypoxic culture in human colorectal cancer-derived Caco2 cells. At the third day of hypoxia, Caco2 cells showed the average increase rate of 2.6 times in ethanolamine plasmalogen and 2.9 times in choline plasmalogen depending on the molecular species compared with those in the second day of hypoxia. In normoxic culture, there was little quantitative change in any species of both ethanolamine and choline plasmalogens for three days. The up-regulations of mRNA of Ca-independent phospholipase Aβ and cytoplasmic phospholipase Aγ as well as the down-regulation of lysoplasmalogenase observed in hypoxia were suggested to be responsible for the increase of plasmalogen in Caco2 cells under hypoxia.
Topics: Caco-2 Cells; Colorectal Neoplasms; Fatty Acids, Unsaturated; Humans; Hypoxia; Phospholipases; Plasmalogens
PubMed: 35468412
DOI: 10.1016/j.bbrc.2022.04.061 -
Chemical Research in Toxicology May 2001
Review
Topics: Animals; Antioxidants; Arachidonic Acid; Eicosanoids; Free Radicals; Humans; Lipid Peroxidation; Mass Spectrometry; Oxidation-Reduction; Plasmalogens
PubMed: 11368542
DOI: 10.1021/tx000250t