Similarly, there are reports that lysophosphatidylcholine may have beneficial effects in rheumatoid arthritis and a number of other diseases. There are also suggestions that some experimental studies of the activity of lysophosphatidylcholines may be flawed because insufficient levels of carrier proteins were used. A further point for consideration is that lysophosphatidylcholine is the precursor of the key lipid mediator lysophosphatidic acid via the action of the enzyme autotaxin in plasma, and this may be the true source of some of the effects described for the former, especially on cell migration and survival.
Hepatic lipase is especially important for generation of these lipids. This finding is now being explored in relation to potential therapeutic applications for neurological diseases, cognitive decline and dementia. Lysophosphatidylcholine has been found to have some functions in cell signalling, and specific receptors coupled to G proteins have been identified, i.
Increased glucose-stimulated insulin secretion has been observed in different cell systems. Lysophosphatidylcholine also activates the mitogen-activated protein kinase in certain cell types, and it promotes demyelination in the nervous system. By interacting with the TRPV4 ion channels of skin keratinocytes, it causes persistent itching. For example, there is reportedly an enrichment of 2-arachidonoyl-lysophosphatidylcholine in carotid atheroma plaque from type 2 diabetic patients.
In vascular endothelial cells, it induces the important pro-inflammatory mediator cyclooxygenase-2 COX-2 , a key enzyme in prostaglandin synthesis. However, it has beneficial effects on the innate immune system as it is able to activate macrophages and increase their phagocytic activity in the presence of T lymphocytes.
As lysophospholipids in general and lysophosphatidylcholine in particular are potent signaling molecules within mammalian cells, their levels are closely regulated, mainly by the action of the lysophospholipases A 1 and A 2 LYPLA1 and LYPLA2 , depending on the position to which the fatty acid is esterified; these are cytosolic serine hydrolases with esterase and thioesterase activity.
The glycerophosphocholine produced can enter the Lands' cycle or be further degraded. In relation to plants, amylose-rich starch granules of cereal grains contain lysophosphatidylcholine as virtually the only lipid in the form of inclusion complexes or lining channels in the macromolecules. Glycerophosphocholine , the fully de-acylated molecule, is produced in the kidney in response to high levels of sodium chloride and has osmoprotective properties. Phosphatidylarsenocholine is a minor component of the lipids of a number of marine organisms and is discussed in the web page dealing with arsenolipids.
Platelet-activating factor PAF or 1-alkylacetyl- sn -glycerophosphocholine is an ether analogue of phosphatidylcholine that has its own web page because of its unique biological properties.
The diatom Nitzschia alba contains a number of interesting sulfonolipids as membrane constituents, including phosphatidylsulfocholine a sulfonium analogue of phosphatidylcholine , i. This novel lipid completely replaces phosphatidylcholine in the organism, but it has subsequently been found in other marine diatoms and algae that also contain phosphatidylcholine per se.
Experiments with isotopically labelled substrates confirmed that both methyl groups and the sulfur atom are derived from methionine. A related lipid, phosphatidyl- S,S -dimethylpropanethiol, has been reported from several algal species. Further sulfolipids, i.
Analysis of phosphatidylcholine presents no particular problems. It is readily isolated by thin-layer or high-performance liquid chromatography methods. Determination of the dipalmitoyl species in lung surfactant is more demanding, but specific methods have been published, and modern mass spectrometry methodology has greatly simplified the task.
Phospholipase A 2 from snake venom is used in methods to determine the position of fatty acids on the glycerol moiety. Lysophosphatidylcholine can be formed inadvertently and over-estimated as a consequence of careless extraction of lipids from tissues.
Phosphatidylcholine and Related Lipids 1. Phosphatidylcholine - Structure and Occurrence Phosphatidylcholine or 1,2-diacyl- sn -glycerophosphocholine once given the trivial name 'lecithin' is a neutral or zwitterionic phospholipid over a pH range from strongly acid to strongly alkaline. Table 1. Positional distribution of fatty acids in the phosphatidylcholine of some animal tissues. Lipid Res.
Lipids , 2 , ; DOI. Table 2. Position Fatty acid Arabidopsis thaliana leaves [1] sn -1 42 4 5 23 26 sn -2 1 trace 5 47 47 Soybean 'lecithin' [2] sn -1 24 9 14 47 4 sn -2 5 1 13 75 6 Lipomyces lipoferus [3] sn -1 24 18 trace 37 16 4 sn -2 4 5 trace 39 31 19 1, Browse, J.
Lipids , 1 , ; DOI. Lipids , 9 , ; DOI. Phosphatidylcholine — Biosynthesis There are several mechanisms for the biosynthesis of phosphatidylcholine in animals, plants and micro-organisms.
Remodelling of Phosphatidylcholine - the Lands' cycle Whatever the mechanism of biosynthesis of phosphatidylcholine in animal tissues, it is apparent that the fatty acid compositions and positional distributions on the glycerol moiety are determined post synthesis by extensive re-modelling involving orchestrated reactions of hydrolysis phospholipase A 2 mainly to lysophosphatidylcholine, acyl-CoA synthesis and re-acylation by lysophospholipid acyltransferases or transacylases, a series of reactions that is sometimes termed the 'Lands' Cycle' after its discoverer W.
Catabolism Phosphatidylcholine and most other glycerophospholipids in membranes can be metabolized by lipolytic enzymes, especially phospholipases, some isoforms of which are specific for particular lipid classes in humans. Phosphatidylcholine — Biological Functions Because of the generally cylindrical shape of the molecule, phosphatidylcholine organizes spontaneously into bilayers, so it is ideally suited to serve as the bulk structural element of biological membranes, and as outlined above it is makes up a high proportion of the lipids in the outer leaflet of the plasma membrane.
Other Phosphatidylcholine Analogues and Metabolites Glycerophosphocholine , the fully de-acylated molecule, is produced in the kidney in response to high levels of sodium chloride and has osmoprotective properties. Analysis Analysis of phosphatidylcholine presents no particular problems. Recommended Reading Botella, C. Importance of phosphatidylcholine on the chloroplast surface. Christie, W. Cornell, R. CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis.
Filkin, S. Phospholipase superfamily: structure, functions, and biotechnological applications. Biochemistry Moscow , 85 , ; DOI. Geiger, O. Phosphatidylcholine biosynthesis and function in bacteria. Acta, Lipids , , ; DOI. Goss, V. Regulation of lung surfactant phospholipid synthesis and metabolism. Hishikawa, D. Diversity and function of membrane glycerophospholipids generated by the remodeling pathway in mammalian cells. Knuplez, E.
An updated review of pro- and anti-inflammatory properties of plasma lysophosphatidylcholines in the vascular system. Lagace, T. The role of phospholipids in the biological activity and structure of the endoplasmic reticulum. Acta, Mol. Cell Res. Law, S. An updated review of lysophosphatidylcholine metabolism in human diseases. McMaster, C. From yeast to humans - roles of the Kennedy pathway for phosphatidylcholine synthesis.
Nakamura, Y. Headgroup biosynthesis of phosphatidylcholine and phosphatidylethanolamine in seed plants. Nilsson, A. Pancreatic and mucosal enzymes in choline phospholipid digestion. Liver Physiol. Patton-Vogt, J. Phospholipid turnover and acyl chain remodeling in the yeast ER. Effect of cholesterol.
Biophys J — Tanaka K, Ohnishi S-I Heterogeneity in the fluidity of intact erythrocyte membrane and its homogenization upon hemolysis. Thompson NL, Axelrod D Reduced lateral mobility of a fluorescent lipid probe in cholesterol-depleted erythrocyte membrane. A combined study using phospholipases and freeze-etching electronmicroscopy.
J Lipids Res — Cell — Wu E-S, Jacobson K, Papahadjopoulos D Lateral diffusion in phospholipid multilayers measured by fluorescence recovery after photobleaching. Comments in molecular and cellular biophys.
Download references. You can also search for this author in PubMed Google Scholar. Reprints and Permissions. Cribier, S. Lateral diffusion of erythrocyte phospholipids in model membranes comparison between inner and outer leaflet components.
Eur Biophys J 18, 33—41 Download citation. Received : 05 June Accepted : 27 September Issue Date : February Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search SpringerLink Search. Abstract The physical properties of lipid bilayers with a similar composition to the outer and inner leaflets of the human erythrocyte membrane have been examined in protein-free model systems. Elsevier, Amsterdam, pp — Google Scholar Cogan U, Schachter D Asymmetry of lipid dynamics in human erythrocyte membranes studied with impermeant fluorophores. Q Rev Biophys —23 Google Scholar Gaffney BJ Practical considerations for the calculation of order parameters for fatty acid or phospholipid spin labels in membranes.
From the cradle to the grave: the role of macrophages in erythropoiesis and erythrophagocytosis. Kamp, D. Inhibition and stimulation of phospholipid scrambling activity. Consequences for lipid asymmetry, echinocytosis, and microvesiculation of erythrocytes. Biochemistry 40 , — Tinmouth, A. The clinical consequences of the red cell storage lesion.
Schroit, A. In vivo recognition and clearance of red blood cells containing phosphatidylserine in their plasma membranes. Leidl, K. Mass spectrometric analysis of lipid species of human circulating blood cells. Acta Mol. Lipids , — Etemadi, A. Membrane asymmetry A survey and critical appraisal of the methodology II.
Methods for assessing the unequal distribution of lipids. Krebs, J. The topology of phospholipids in artificial and biological membranes. Organization of phospholipids in human red cell membranes as detected by the action of various purified phospholipases.
Demel, R. Relation between various phospholipase actions on human red cell membranes and the interfacial phospholipid pressure in monolayers. Szejtli, J. Introduction and general overview of cyclodextrin chemistry.
Cheng, H. Preparation and properties of asymmetric vesicles that mimic cell membranes effect upon lipid raft formation and transmembrane helix orientation. Huang, Z. Effect of cyclodextrin and membrane lipid structure upon cyclodextrin—lipid interaction. Langmuir 29 , — London, E. Zidovetzki, R. Use of cyclodextrins to manipulate plasma membrane cholesterol content: evidence, misconceptions and control strategies.
Doktorova, M. Preparation of asymmetric phospholipid vesicles for use as cell membrane models. Vahedi, A. Kainu, V. Introduction of phospholipids to cultured cells with cyclodextrin. Lipid Res. Replacing plasma membrane outer leaflet lipids with exogenous lipid without damaging membrane integrity. PloS One 14 , e Moreno, M. Translocation of phospholipids and dithionite permeability in liquid-ordered and liquid-disordered membranes.
Bligh, E. A rapid method of total lipid extraction and purification. Ramstedt, B. Analysis of natural and synthetic sphingomyelins using high-performance thin-layer chromatography. Schlegel, R. Phosphatidylserine, a death knell. Cell Death Differ. Hess, J. An update on solutions for red cell storage. Vox Sang. Lu, C. Procoagulant activity of long-term stored red blood cells due to phosphatidylserine exposure. Dasgupta, S. Lactadherin binding and phosphatidylserine expression on cell surface-comparison with annexin A5.
Dinkla, S. Phosphatidylserine exposure on stored red blood cells as a parameter for donor-dependent variation in product quality. Blood Transfus. Gebran, S. A modified colorimetric method for the measurement of phagocytosis and antibody-dependent cell cytotoxicity using 2, 7-diaminofluorene.
Fauvelle, F. The two-step extraction of phosphatidylinositol from the membrane. Debouzy, J. A study of the factors controlling the association with serine-, ethanolamine-, and choline-phospholipids. Aittoniemi, J. Insight into the putative specific interactions between cholesterol, sphingomyelin, and palmitoyl-oleoyl phosphatidylcholine. Tsamaloukas, A. Thermodynamic comparison of the interactions of cholesterol with unsaturated phospholipid and sphingomyelins.
The preferential interaction of cholesterol with different classes of phospholipids. Ohvo, H. Effects of sphingomyelin and phosphatidylcholine degradation on cyclodextrin-mediated cholesterol efflux in cultured fibroblasts. Steck, T. Transverse distribution of plasma membrane bilayer cholesterol: picking sides. Traffic 19 , — Probing red cell membrane cholesterol movement with cyclodextrin.
Bennett, W. Molecular view of cholesterol flip-flop and chemical potential in different membrane environments. Devaux, P. Transmembrane asymmetry and lateral domains in biological membranes. Traffic 5 , — Lipid organization of the plasma membrane. Ohtani, Y. Narayanan, S. Wheat leaf lipids during heat stress: I. High day and night temperatures result in major lipid alterations. Plant Cell Environ. Starr, T. The phorbol myristateacetate differentiation protocol is critical to the interaction of THP-1 macrophages with Salmonella Typhimurium.
PloS One 13 , e Download references. You can also search for this author in PubMed Google Scholar. Correspondence to Amir M. A provisional patent application has been submitted on methods to extend the storage shelf life of red blood cells.
The authors declare no other competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.
If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Reprints and Permissions. Quantitative analysis of red blood cell membrane phospholipids and modulation of cell-macrophage interactions using cyclodextrins. Sci Rep 10, Download citation. Received : 03 May Accepted : 21 August Published : 15 September Anyone you share the following link with will be able to read this content:.
Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
Advanced search. Skip to main content Thank you for visiting nature. Download PDF. Subjects Lipidomics Lipids Membrane lipids Membrane structure and assembly. Abstract The plasma membrane of eukaryotic cells is asymmetric with respect to its phospholipid composition. Introduction The mammalian cell membrane is an asymmetric structure, with distinct lipids localizing in each leaflet of the membrane bilayer. Results Optimization of the lipid exchange process To extract phospholipids from the RBC outer leaflet, a process adapted from Li et al.
Table 1 The optimized conditions used for the lipid exchange process. Full size table. Figure 1. Full size image. Figure 2. Figure 3. Figure 4. Figure 5. Discussion While the phospholipid asymmetry of the RBC plasma membrane has been known for more than 40 years, methods to analyze the outer leaflet lipid composition still depend on enzymatic degradation of the outer leaflet lipids.
Phospholipid exchange using cyclodextrins Different amounts of various phospholipids as reported in Table 1 and Supplementary Table S1 were first dried out of their organic solvents using a SpeedVac Thermo Fisher Scientific, Waltham, MA.
Measuring the hemolysis of RBCs Presence of hemoglobin in the exchange solution was used as a measure of RBC membrane disruption hemolysis. Identification of extracted and delivered phospholipids As phospholipid exchange proceeds, exogenous phospholipids are delivered to the membrane, replacing the endogenous phospholipids of the outer leaflet of RBCs. Confocal microscopy of RBCs after exchange with a fluorescent lipid Delivery of phospholipids to the membrane was studied using fluorescence.
Mass spectrometry analysis of the lipids Quantification of the phospholipids and their respective species were performed using mass spectrometry. Detection of PS on the outer leaflet before and after exchange Presence of PS in the outer leaflet of the mammalian cells is attributed to the apoptosis of the cells.
References 1. CAS Google Scholar 3.
0コメント