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Membranes Aug 2023Plasmalogens are a unique family of cellular glycerophospholipids that contain a vinyl-ether bond. The synthesis of plasmalogens is initiated in peroxisomes and... (Review)
Review
Plasmalogens are a unique family of cellular glycerophospholipids that contain a vinyl-ether bond. The synthesis of plasmalogens is initiated in peroxisomes and completed in the endoplasmic reticulum. Plasmalogens are transported to the post-Golgi compartment, including endosomes and plasma membranes, in a manner dependent on ATP, but not vesicular transport. Plasmalogens are preferentially localized in the inner leaflet of the plasma membrane in a manner dependent on P4-type ATPase ATP8B2, that associates with the CDC50 subunit. Plasmalogen biosynthesis is spatiotemporally regulated by a feedback mechanism that senses the amount of plasmalogens in the inner leaflet of the plasma membrane and controls the stability of fatty acyl-CoA reductase 1 (FAR1), the rate-limiting enzyme for plasmalogen biosynthesis. The physiological consequences of such asymmetric localization and homeostasis of plasmalogens are discussed in this review.
PubMed: 37755186
DOI: 10.3390/membranes13090764 -
Biomolecules Apr 2023Plasmalogens are membrane phospholipids with two fatty acid hydrocarbon chains linked to L-glycerol, one containing a characteristic cis-vinyl ether function and the...
Plasmalogens are membrane phospholipids with two fatty acid hydrocarbon chains linked to L-glycerol, one containing a characteristic cis-vinyl ether function and the other one being a polyunsaturated fatty acid (PUFA) residue linked through an acyl function. All double bonds in these structures display the cis geometrical configuration due to desaturase enzymatic activity and they are known to be involved in the peroxidation process, whereas the reactivity through cis-trans double bond isomerization has not yet been identified. Using 1-(1Z-octadecenyl)-2-arachidonoyl--glycero-3-phosphocholine (C18 plasm-20:4 PC) as a representative molecule, we showed that the cis-trans isomerization can occur at both plasmalogen unsaturated moieties, and the product has characteristic analytical signatures useful for omics applications. Using plasmalogen-containing liposomes and red blood cell (RBC) ghosts under biomimetic Fenton-like conditions, in the presence or absence of thiols, peroxidation, and isomerization processes were found to occur with different reaction outcomes due to the particular liposome compositions. These results allow gaining a full scenario of plasmalogen reactivity under free radical conditions. Moreover, clarification of the plasmalogen reactivity under acidic and alkaline conditions was carried out, identifying the best protocol for RBC membrane fatty acid analysis due to their plasmalogen content of 15-20%. These results are important for lipidomic applications and for achieving a full scenario of radical stress in living organisms.
Topics: Plasmalogens; Isomerism; Fatty Acids; Liposomes; Free Radicals; Erythrocyte Membrane
PubMed: 37238600
DOI: 10.3390/biom13050730 -
Frontiers in Cell and Developmental... 2020Plasmalogens are a special class of polar glycerolipids containing a vinyl-ether bond and an ester bond at sn-1 and sn-2 positions of the glycerol backbone,... (Review)
Review
Plasmalogens are a special class of polar glycerolipids containing a vinyl-ether bond and an ester bond at sn-1 and sn-2 positions of the glycerol backbone, respectively. In animals, impaired biosynthesis and regulation of plasmalogens may lead to certain neurological and metabolic diseases. Plasmalogens deficiency was proposed to be strongly associated with neurodegenerative and metabolic diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), and appropriate supplement of plasmalogens could help to prevent and possibly provide therapy of these diseases. Plasmalogens evolved first in anaerobic bacteria with an anaerobic biosynthetic pathway. Later, an oxygen-dependent biosynthesis of plasmalogens appeared in animal cells. This review summarizes and updates current knowledge of anaerobic and aerobic pathways of plasmalogens biosynthesis, including the enzymes involved, steps and aspects of the regulation of these processes. Strategies for increasing the expression of plasmalogen synthetic genes using synthetic biology techniques under specific conditions are discussed. Deep understanding of plasmalogens biosynthesis will provide the bases for the use of plasmalogens and their precursors as potential therapeutic regimens for age-related degenerative and metabolic diseases.
PubMed: 32984309
DOI: 10.3389/fcell.2020.00765 -
Analytica Chimica Acta Nov 2021Changes in plasmalogen glycerophosphoethanolamine (PE-P) composition (structure and abundance) are a key indicator of altered lipid metabolism. Differential changes in...
Changes in plasmalogen glycerophosphoethanolamine (PE-P) composition (structure and abundance) are a key indicator of altered lipid metabolism. Differential changes in the levels of PE-P have been reported in different disease states, including neurodegenerative diseases. Of particular interest, traumatic brain injury (TBI) has resulted in altered expression of glycerophospholipid profiles, including PE-P. To date, most analytical assays assessing PE-P have focused on general lipidomic workflows to evaluate the relative, semi-quantitative abundance of PE-P during disease progression. This approach provides a broad evaluation of PE-P, yet often lacks specificity and sensitivity for individual PE-P structures which is a necessity for robust quantitative data. The present study highlights the development of a targeted, quantitative method using a HILIC separation and selective reaction monitoring mass spectrometry for the confident identification and accurate quantitation of PE-P. Our innovative method incorporates both the sn-1 alkyl vinyl ether and sn-2 acyl chain as product ion transitions, for specific and sensitive quantitation of 100 PE-P structures. Our method also uniquely allowed for the unambiguous assignment and quantitation of di-unsaturated sn-1 PE-P structures, which to date have not been conclusively quantified. Application of this assay to a TBI mouse model resulted in distinct temporal profiles for plasma PE-P up to 28 days post injury. Plasma PE-P were significantly increased 24 h after induced TBI, followed by a gradual reduction to sham concentrations by day 28. Overall, we established a structure-specific, quantitative assay for identification and quantitation of a comprehensive set of PE-P structures with demonstrated relevance to brain injury.
Topics: Animals; Lipidomics; Mass Spectrometry; Mice; Phosphatidylethanolamines; Plasmalogens
PubMed: 34756256
DOI: 10.1016/j.aca.2021.339088 -
Frontiers in Cell and Developmental... 2023Sperm are terminally differentiated cells that lack most of the membranous organelles, resulting in a high abundance of ether glycerolipids found across different... (Review)
Review
Sperm are terminally differentiated cells that lack most of the membranous organelles, resulting in a high abundance of ether glycerolipids found across different species. Ether lipids include plasmalogens, platelet activating factor, GPI-anchors and seminolipid. These lipids play important roles in sperm function and performance, and thus are of special interest as potential fertility markers and therapeutic targets. In the present article, we first review the existing knowledge on the relevance of the different types of ether lipids for sperm production, maturation and function. To further understand ether-lipid metabolism in sperm, we then query available proteomic data from highly purified sperm, and produce a map of metabolic steps retained in these cells. Our analysis pinpoints the presence of a truncated ether lipid biosynthetic pathway that would be competent for the production of precursors through the initial peroxisomal core steps, but devoid of subsequent microsomal enzymes responsible for the final synthesis of all complex ether-lipids. Despite the widely accepted notion that sperm lack peroxisomes, the thorough analysis of published data conducted herein identifies nearly 70% of all known peroxisomal resident proteins as part of the sperm proteome. In view of this, we highlight open questions related to lipid metabolism and possible peroxisomal functions in sperm. We propose a repurposed role for the truncated peroxisomal ether-lipid pathway in detoxification of products from oxidative stress, which is known to critically influence sperm function. The likely presence of a peroxisomal-derived remnant compartment that could act as a sink for toxic fatty alcohols and fatty aldehydes generated by mitochondrial activity is discussed. With this perspective, our review provides a comprehensive metabolic map associated with ether-lipids and peroxisomal-related functions in sperm and offers new insights into potentially relevant antioxidant mechanisms that warrant further research.
PubMed: 37397249
DOI: 10.3389/fcell.2023.1166232 -
Food Chemistry Aug 2020Plasmalogens are dietary phospholipids with beneficial health effects. In this work, plasmalogen characteristics and changes in beef during boiling, frying, and roasting...
Plasmalogens are dietary phospholipids with beneficial health effects. In this work, plasmalogen characteristics and changes in beef during boiling, frying, and roasting were comprehensively investigated by liquid-chromatography-mass spectrometry. The alteration of plasmalogen fingerprint during cooking processes was found by untargeted omics approach, in which time of boiling, temperature of roasting, and meat core/surface of frying were responsible for the observed variations. Moreover, the targeted determination of representative plasmalogen species showed significant loss with a temperature- and time-dependent manner in roasting and frying. And frying even showed an extra loss in meat surface compared with core. Furthermore, an artificial neural network-based predictive model elucidated the dynamics of plasmalogen species during cooking. Finally, batter-coating pretreatment was performed to show its protection against plasmalogens loss during frying. These results might provide a potential strategy to better control and improve the quality of functional foodstuffs during cooking processes.
Topics: Animals; Cattle; Chromatography, High Pressure Liquid; Cooking; Food Analysis; Hot Temperature; Neural Networks, Computer; Plasmalogens; Red Meat; Tandem Mass Spectrometry; Transition Temperature
PubMed: 32325364
DOI: 10.1016/j.foodchem.2020.126764 -
International Journal of Molecular... Jul 2023Adult hippocampal neurogenesis (AHN) is associated with hippocampus-dependent cognitive function, and its initiation is attributed to neural stem cells (NSCs)....
Adult hippocampal neurogenesis (AHN) is associated with hippocampus-dependent cognitive function, and its initiation is attributed to neural stem cells (NSCs). Dysregulated AHN has been identified in Alzheimer's disease (AD) and may underlie impaired cognitive function in AD. Modulating the function of NSCs and stimulating AHN are potential ways to manipulate AD. Plasmalogen (PLA) are a class of cell membrane glycerophospholipids which exhibit neuroprotective properties. However, the effect of PLA on altered AHN in AD has not been investigated. In our study, PLA(10μg/mL) -attenuated Aβ (1-42) (5μM) induced a decrease in NSC viability and neuronal differentiation of NSCs, partially through regulating the Wnt/β-catenin pathway. Additionally, AD mice were supplemented with PLA (67mg/kg/day) for 6 weeks. PLA treatment improved the impaired AHN in AD mice, including increasing the number of neural stem cells (NSCs) and newly generated neurons. The memory function of AD mice was also enhanced after PLA administration. Therefore, it was summarized that PLA could regulate NSC differentiation by activating the Wnt/β-catenin pathway and ameliorate AD-related memory impairment through up-regulating AHN.
PubMed: 37569610
DOI: 10.3390/ijms241512234 -
Biochimica Et Biophysica Acta.... Apr 2023Alkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1) are enzymes involved in ether lipid metabolism. While AGMO degrades plasmanyl lipids by...
Alkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1) are enzymes involved in ether lipid metabolism. While AGMO degrades plasmanyl lipids by oxidative cleavage of the ether bond, PEDS1 exclusively synthesizes a specific subclass of ether lipids, the plasmalogens, by introducing a vinyl ether double bond into plasmanylethanolamine phospholipids. Ether lipids are characterized by an ether linkage at the sn-1 position of the glycerol backbone and they are found in membranes of different cell types. Decreased plasmalogen levels have been associated with neurological diseases like Alzheimer's disease. Agmo-deficient mice do not present an obvious phenotype under unchallenged conditions. In contrast, Peds1 knockout mice display a growth phenotype. To investigate the molecular consequences of Agmo and Peds1 deficiency on the mouse lipidome, five tissues from each mouse model were isolated and subjected to high resolution mass spectrometry allowing the characterization of up to 2013 lipid species from 42 lipid subclasses. Agmo knockout mice moderately accumulated plasmanyl and plasmenyl lipid species. Peds1-deficient mice manifested striking changes characterized by a strong reduction of plasmenyl lipids and a concomitant massive accumulation of plasmanyl lipids resulting in increased total ether lipid levels in the analyzed tissues except for the class of phosphatidylethanolamines where total levels remained remarkably constant also in Peds1 knockout mice. The rate-limiting enzyme in ether lipid metabolism, FAR1, was not upregulated in Peds1-deficient mice, indicating that the selective loss of plasmalogens is not sufficient to activate the feedback mechanism observed in total ether lipid deficiency.
Topics: Animals; Mice; Plasmalogens; Lipid Metabolism; Lipidomics; Ethers; Mice, Knockout
PubMed: 36690320
DOI: 10.1016/j.bbalip.2023.159285 -
Integrative Medicine (Encinitas, Calif.) Jun 2020A critical factor involved in the pathophysiology of Alzheimer's disease (AD) and related dementias is the decline of plasmalogens, a key glycerophospholipid required... (Review)
Review
A critical factor involved in the pathophysiology of Alzheimer's disease (AD) and related dementias is the decline of plasmalogens, a key glycerophospholipid required for normal neuron function. An accumulating body of evidence correlates low blood and brain plasmalogens with higher levels of AD pathology and lower cognition scores and indicates that declines in these phospholipids begin years before clinical symptoms develop. Furthermore, it has been recently reported that high blood plasmalogen levels neutralize the increased risk of dementia in persons who carry the APOE epsilon 4 allele, the most significant genetic risk factor for AD. There are over 30 common species of plasmalogens in the human body with different plasmalogen species playing different roles, depending on the organ and cell type. Accordingly, there is great interest in understanding how to selectively target plasmalogen augmentation for specific health needs. For example, brain white matter is comprised of plasmalogens containing monounsaturated fatty acids, whereas gray matter is comprised of plasmalogens containing polyunsaturated fatty acids. Fortunately, the structure-activity and biochemistry of plasmalogen augmentation has been extensively studied in cell and animal models. Restoring and augmenting levels of selective plasmalogens can be achieved with dietary supplementation of 1-O-alkyl-2-acyl glycerol oils containing the desired fatty acid type at the 2-acyl position. Neuron-targeted 1-O-alkyl-2-acyl glycerol containing DHA has been shown to be neuroprotective and neuroactive in animal models of neurodegeneration. This review will discuss the mechanisms by which plasmalogen deficiency leads to Alzheimer's and/or dementia and the critical role that 1-O-alkyl-2-acyl glycerol oils can play in patients with those disorders.
PubMed: 33132773
DOI: No ID Found -
MedRxiv : the Preprint Server For... Jul 2020We performed RNA-Seq and high-resolution mass spectrometry on 128 blood samples from COVID-19 positive and negative patients with diverse disease severities. Over 17,000...
We performed RNA-Seq and high-resolution mass spectrometry on 128 blood samples from COVID-19 positive and negative patients with diverse disease severities. Over 17,000 transcripts, proteins, metabolites, and lipids were quantified and associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a comparative analysis with published data and a machine learning approach for prediction of COVID-19 severity.
PubMed: 32743614
DOI: 10.1101/2020.07.17.20156513