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Journal of the American Society For... May 2006The covalent interactions between peptides and lipid oxidation products, with formation of Schiff and Michael adducts, are known to occur during free radical oxidative...
The covalent interactions between peptides and lipid oxidation products, with formation of Schiff and Michael adducts, are known to occur during free radical oxidative damage. In this study, leucine-enkephalin-glycerophosphatidylcholine alka(e)nal adducts were analyzed by electrospray tandem mass spectrometry (MS/MS). Upon collision-induced dissociation of the Leucine enkephalin-2-(9-oxo-nonanoyl)-1-palmitoyl-3-glycerophosphatidylcholine, an alkanal Schiff adduct observed at m/z 1187.7, the main product ions were attributed to the phosphocholine polar head and loss of the peptide. Also, product ions resulting from characteristic losses of phosphatidylcholines and cleavages of the peptide chain (mainly b-type) were observed. Additional product ions formed by combined peptide and phosphatidylcholine fragmentations were identified. The fragmentation pattern of the leucine enkephalin-alkanal Schiff adduct and the leucine enkephalin-alkenal phosphatidylcholine Schiff and Michael adducts were similar, although the loss of the peptide for the Michael adduct should occur through a distinct mechanism. These fragmentation pathways differ greatly from those described for peptide-lipid Schiff and Michael adducts, in which only peptide chain cleavages are reported, probably due to charge retention in the glycerophosphatidylcholine polar head in peptide-glycerophosphatidylcholine adducts.
Topics: Cross-Linking Reagents; Enkephalin, Leucine; Neurotransmitter Agents; Peptides; Phosphatidylcholines; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 16517179
DOI: 10.1016/j.jasms.2006.01.006 -
Journal of Lipid Research Feb 1993It has previously been shown that the hydrolysis of high density lipoprotein (HDL) phospholipids by hepatic lipase promotes the hepatic uptake of triglyceride and...
It has previously been shown that the hydrolysis of high density lipoprotein (HDL) phospholipids by hepatic lipase promotes the hepatic uptake of triglyceride and cholesteryl ester from HDL. Since the hydrolysis of HDL phospholipids promotes HDL cholesteryl ester uptake, then it is possible that the hepatic metabolism of HDL could be altered by changing the molecular species composition of HDL phosphatidylcholine (PC) (the major phospholipid in HDL). To test this possibility the uptake of [3H]triolein and [14C]cholesteryl oleate by the isolated perfused rat liver was determined in a nonrecirculating perfusion system following a bolus injection of reconstituted HDL (rHDL) prepared with rat serum HDL apolipoproteins, [3H]triolein, [14C]cholesteryl oleate, unesterified cholesterol, and one of five molecular species of phosphatidylcholine (16:0-18:2, 16:1-16:1, 18:0-18:2, 18:1-16:0, or 20:1-20:1), 18:1-16:0 phosphatidylcholine diether, or the total phosphatidylcholine fraction isolated from rat serum HDL. The apolipoprotein profiles and lipid compositions of all the rHDL were similar. The greatest uptake of [3H]triolein was obtained with the rHDL prepared with 16:0-18:2 phosphatidylcholine. The amount of [3H]triolein taken up by the liver when the rHDL were prepared with 16:1-16:1, 18:0-18:2, 18:1-16:0, 20:1-20:1, 18:1-16:0 phosphatidylcholine diether, or rat serum HDL phosphatidylcholine was 56.7%, 51.7, 39.9%, 27.6%, 31.8%, and 84.7%, respectively, of the amount taken up from the rHDL prepared with 16:0-18:2 phosphatidylcholine. Likewise, the greatest amount of [14C]cholesteryl oleate was taken up by the liver when the rHDL was prepared with 16:0-18:2 phosphatidylcholine and the variation in [14C]cholesteryl oleate uptake from the various rHDL displayed a pattern of dependence on the phosphatidylcholine molecular species of rHDL similar to triolein uptake. The variation in the rate of rHDL phosphatidylcholine hydrolysis by hepatic lipase in vitro as a function of the PC molecular species composition of the rHDL also resembled the variation in the hepatic uptake of [14C]cholesteryl oleate and [3H]triolein. Partial substitution of rHDL phosphatidylcholine with the minor phospholipids isolated from rat serum HDL affected neither the hepatic uptake of [3H]triolein or [14C]cholesteryl oleate nor phosphatidylcholine hydrolysis by hepatic lipase in vitro when 16:0-18:2 phosphatidylcholine or rat serum HDL phosphatidylcholine was used to prepare the rHDL. On the other hand, when rHDL was prepared with 20:1-20:1 phosphatidylcholine, the inclusion of the minor phospholipids increased [3H]triolein and [14C]cholesteryl oleate uptake and phosphatidylcholine hydrolysis approximately twofold.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Carbon Radioisotopes; Cholesterol Esters; Electrophoresis, Polyacrylamide Gel; Hydrolysis; Lipoproteins, HDL; Liver; Male; Phosphatidylcholines; Rats; Rats, Sprague-Dawley; Triglycerides; Triolein; Tritium
PubMed: 8429254
DOI: No ID Found -
Biochimica Et Biophysica Acta.... Nov 2021Due to the increasing number of infections together with the appearance of bacteria exhibiting multi-drug resistance, new antibiotics are being sought. In this context...
Due to the increasing number of infections together with the appearance of bacteria exhibiting multi-drug resistance, new antibiotics are being sought. In this context the interest of the cationic lipoids increases because of their amphiphilic structure and positive charge that can stimulates the antibacterial action of these compounds. Thus, in this work we have performed the studies on the effect of one selected triesters of phosphatidylcholine, namely 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine (EDPPC), on the model lipid membranes. The investigations included the analysis of the impact of EDPPC on multicomponent monolayers and bilayers consisting of the lipids naturally occurring in bacterial membranes (phosphatidylethanolamines (PE), phosphatidylglycerols (PG) and cardiolipin (CL)), mixed in proportions reflecting the lipid composition of these biomembranes. In the study, the Langmuir monolayers (registered on water and PBS buffer) and liposomes as model bacterial biomembranes were applied. The obtained results demonstrate that the presence of cationic lipoid in PE/PG and PE/PG/CL systems significantly modifies their properties and molecular organization. The incorporation of EDPPC into model bacterial membranes primarily impact on the intermolecular interactions. It was shown that the strength of the interaction between the cationic lipid and the components of the model membranes depends both on the composition of the membrane as well as on the type of subphase. Furthermore, the investigated cationic lipoid leads to the decrease of the ordering of acyl chains and thus to the increase of fluidity of membranes. The obtained results allow one to propose that EDPPC may behave as antibiotic active at the level of membrane.
Topics: Biological Transport; Esters; Fluorescence Polarization; Membranes, Artificial; Phosphatidylcholines; Thermodynamics
PubMed: 34343534
DOI: 10.1016/j.bbamem.2021.183711 -
Biophysical Journal Dec 2003In recent years, the implication of sphingomyelin in lipid raft formation has intensified the long sustained interest in this membrane lipid. Accumulating evidences show...
In recent years, the implication of sphingomyelin in lipid raft formation has intensified the long sustained interest in this membrane lipid. Accumulating evidences show that cholesterol preferentially interacts with sphingomyelin, conferring specific physicochemical properties to the bilayer membrane. The molecular packing created by cholesterol and sphingomyelin, which presumably is one of the driving forces for lipid raft formation, is known in general to differ from that of cholesterol and phosphatidylcholine membranes. However, in many studies, saturated phosphatidylcholines are still considered as a model for sphingolipids. Here, we investigate the effect of cholesterol on mixtures of dioleoyl-phosphatidylcholine (DOPC) and dipalmitoyl-phosphatidylcholine (DPPC) or distearoyl-phosphatidylcholine (DSPC) and compare it to that on mixtures of DOPC and sphingomyelin analyzed in previous studies. Giant unilamellar vesicles prepared from ternary mixtures of various lipid compositions were imaged by confocal fluorescence microscopy and, within a certain range of sterol content, domain formation was observed. The assignment of distinct lipid phases and the molecular mobility in the membrane bilayer was investigated by fluorescence correlation spectroscopy. Cholesterol was shown to affect lipid dynamics in a similar way for DPPC and DSPC when the two phospholipids were combined with cholesterol in binary mixtures. However, the corresponding ternary mixtures exhibited different spatial lipid organization and dynamics. Finally, evidences of a weaker interaction of cholesterol with saturated phosphatidylcholines than with sphingomyelin (with matched chain length) are discussed.
Topics: 1,2-Dipalmitoylphosphatidylcholine; Biophysical Phenomena; Biophysics; Cell Membrane; Cholesterol; Diffusion; Lipid Bilayers; Lipids; Microscopy, Confocal; Models, Statistical; Phosphatidylcholines; Protein Structure, Tertiary
PubMed: 14645066
DOI: 10.1016/S0006-3495(03)74791-2 -
PLoS Pathogens Jul 2023Glycerophospholipids including phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are vital components of biological membranes. Trypanosomatid parasites of the...
Glycerophospholipids including phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are vital components of biological membranes. Trypanosomatid parasites of the genus Leishmania can acquire PE and PC via de novo synthesis and the uptake/remodeling of host lipids. In this study, we investigated the ethanolaminephosphate cytidylyltransferase (EPCT) in Leishmania major, which is the causative agent for cutaneous leishmaniasis. EPCT is a key enzyme in the ethanolamine branch of the Kennedy pathway which is responsible for the de novo synthesis of PE. Our results demonstrate that L. major EPCT is a cytosolic protein capable of catalyzing the formation of CDP-ethanolamine from ethanolamine-phosphate and cytidine triphosphate. Genetic manipulation experiments indicate that EPCT is essential in both the promastigote and amastigote stages of L. major as the chromosomal null mutants cannot survive without the episomal expression of EPCT. This differs from our previous findings on the choline branch of the Kennedy pathway (responsible for PC synthesis) which is required only in promastigotes but not amastigotes. While episomal EPCT expression does not affect promastigote proliferation under normal conditions, it leads to reduced production of ethanolamine plasmalogen or plasmenylethanolamine, the dominant PE subtype in Leishmania. In addition, parasites with episomal EPCT exhibit heightened sensitivity to acidic pH and starvation stress, and significant reduction in virulence. In summary, our investigation demonstrates that proper regulation of EPCT expression is crucial for PE synthesis, stress response, and survival of Leishmania parasites throughout their life cycle.
Topics: Leishmania major; Ethanolamines; Ethanolamine; Phosphatidylcholines; Homeostasis
PubMed: 37506172
DOI: 10.1371/journal.ppat.1011112 -
The Journal of Membrane Biology Oct 2017The degree of lipid unsaturation is a parameter used to describe membrane susceptibility to oxidation. This paper highlights the importance of double bond distribution...
The degree of lipid unsaturation is a parameter used to describe membrane susceptibility to oxidation. This paper highlights the importance of double bond distribution in the hydrophobic parts of lipid layers. The problem was studied by determining the effects induced by ozone dissolved in an aqueous phase acting on layers of unsaturated cholines of various molecular structures, including bi-unsaturated (DOPC), mono-unsaturated (POPC) and natural origin (soy PC). The destructive effects of ozone were quantified as the ratio of areas per molecule, which corresponded to a 1 mN/m rise in the layer surface pressure for oxidized to non-oxidized lipids (A /A ). The experimental results showed different behaviours among the studied lipids. Layers of DOPC with both unsaturated fatty acyl chains exhibited the greatest disruption compared with that of PC extracted from soy, which maintained stability despite high degree of unsaturation. Mono-unsaturated ozonized layers of POPC did not exhibit any disruption, but their modified properties indicated structural changes caused by the appearance of oxidation products. The stability of mixed layers (of the same unsaturation degree as the soy PC) composed of DOPC and fully saturated lipid increased, however, not reaching the soy PC level. Comparisons of the behaviour of tested systems indicated that the fraction of lipids containing one saturated acyl chain is the parameter most important for stability of the oxidized layer. The stabilizing effects of the cholesterol admixture were also quantified. Results obtained for lipid layers were supported by measurements of liposome size, zeta potential and surface tension of liposome suspension.
Topics: Membranes, Artificial; Oxidation-Reduction; Ozone; Phosphatidylcholines
PubMed: 28799139
DOI: 10.1007/s00232-017-9976-8 -
Increased expression of phosphatidylcholine (16:0/18:1) and (16:0/18:2) in thyroid papillary cancer.PloS One 2012A good prognosis can be expected for most, but not all, cases of thyroid papillary cancer. Numerous molecular studies have demonstrated beneficial treatment and...
A good prognosis can be expected for most, but not all, cases of thyroid papillary cancer. Numerous molecular studies have demonstrated beneficial treatment and prognostic factors in various molecular markers. Whereas most previous reports have focused on genomics and proteomics, few have focused on lipidomics. With the advent of mass spectrometry (MS), it has become possible to identify many types of molecules, and this analytical tool has become critical in the field of omics. Recently, imaging mass spectrometry (IMS) was developed. After a simple pretreatment process, IMS can be used to examine tissue sections on glass slides with location information.Here, we conducted an IMS analysis of seven cases of thyroid papillary cancer by comparison of cancerous with normal tissues, focusing on the distribution of phospholipids. We identified that phosphatidylcholine (16:0/18:1) and (16:0/18:2) and sphingomyelin (d18:0/16:1) are significantly higher in thyroid papillary cancer than in normal thyroid tissue as determined by tandem mass (MS/MS) analysis. These distributional differences may be associated with the biological behavior of thyroid papillary cancer.
Topics: Carcinoma; Carcinoma, Papillary; Female; Humans; Male; Middle Aged; Phosphatidylcholines; Staining and Labeling; Tandem Mass Spectrometry; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 23139822
DOI: 10.1371/journal.pone.0048873 -
The Journal of Physical Chemistry. B Jun 2010A significant modification to the additive all-atom CHARMM lipid force field (FF) is developed and applied to phospholipid bilayers with both choline and ethanolamine...
A significant modification to the additive all-atom CHARMM lipid force field (FF) is developed and applied to phospholipid bilayers with both choline and ethanolamine containing head groups and with both saturated and unsaturated aliphatic chains. Motivated by the current CHARMM lipid FF (C27 and C27r) systematically yielding values of the surface area per lipid that are smaller than experimental estimates and gel-like structures of bilayers well above the gel transition temperature, selected torsional, Lennard-Jones and partial atomic charge parameters were modified by targeting both quantum mechanical (QM) and experimental data. QM calculations ranging from high-level ab initio calculations on small molecules to semiempirical QM studies on a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer in combination with experimental thermodynamic data were used as target data for parameter optimization. These changes were tested with simulations of pure bilayers at high hydration of the following six lipids: DPPC, 1,2-dimyristoyl-sn-phosphatidylcholine (DMPC), 1,2-dilauroyl-sn-phosphatidylcholine (DLPC), 1-palmitoyl-2-oleoyl-sn-phosphatidylcholine (POPC), 1,2-dioleoyl-sn-phosphatidylcholine (DOPC), and 1-palmitoyl-2-oleoyl-sn-phosphatidylethanolamine (POPE); simulations of a low hydration DOPC bilayer were also performed. Agreement with experimental surface area is on average within 2%, and the density profiles agree well with neutron and X-ray diffraction experiments. NMR deuterium order parameters (S(CD)) are well predicted with the new FF, including proper splitting of the S(CD) for the aliphatic carbon adjacent to the carbonyl for DPPC, POPE, and POPC bilayers. The area compressibility modulus and frequency dependence of (13)C NMR relaxation rates of DPPC and the water distribution of low hydration DOPC bilayers also agree well with experiment. Accordingly, the presented lipid FF, referred to as C36, allows for molecular dynamics simulations to be run in the tensionless ensemble (NPT), and is anticipated to be of utility for simulations of pure lipid systems as well as heterogeneous systems including membrane proteins.
Topics: 1,2-Dipalmitoylphosphatidylcholine; Dimyristoylphosphatidylcholine; Lipid Bilayers; Lipids; Molecular Dynamics Simulation; Phosphatidylcholines; Phosphatidylethanolamines; Quantum Theory; Thermodynamics; X-Ray Diffraction
PubMed: 20496934
DOI: 10.1021/jp101759q -
Nutrients Oct 2019Chrysin-loaded phytosomes (CP) were prepared using either soya phosphatidylcholine (SPC) or egg phospholipid (EPL) by the solvent evaporation method. Different...
Chrysin-loaded phytosomes (CP) were prepared using either soya phosphatidylcholine (SPC) or egg phospholipid (EPL) by the solvent evaporation method. Different phospholipid matrices resulted in significant differences in size, mechanical property and solubility of the CP. The most stable CP was obtained with EPL at a molar ratio of 1:3 (chrysin: EPL, CEP-1:3). CEP-1:3 displayed an average size of 117 nm with uniform size distribution (polydispersity index: 0.30) and zeta potential of -31 mV. A significantly greater elastic modulus of CEP-1:3 (2.7-fold) indicated tighter packing and strong molecular bonding than those of CP prepared with SPC (CSP-1:3). X-ray diffraction and Fourier transform infrared spectroscopic analysis of CEP-1:3 confirmed molecular complexation. CEP-1:3 displayed a greater glucose uptake promoting effect than free chrysin and CSP-1:3 in muscle cells by stimulating gene expression of peroxisome proliferator-activated receptor γ and glucose transporter type 4. The results of the present study suggest that the phospholipid matrix used for the preparation of phytosomes critically influences their performance.
Topics: Animals; Cell Line; Flavonoids; Glucose; Liposomes; Mice; Phosphatidylcholines; Phospholipids; Solubility
PubMed: 31652637
DOI: 10.3390/nu11102549 -
Biochimica Et Biophysica Acta.... Feb 2020The triesters of phosphatidylcholine as the derivatives of natural phosphatidylcholines are less cytotoxic than the other cationic lipoids, therefore they can be applied...
The triesters of phosphatidylcholine as the derivatives of natural phosphatidylcholines are less cytotoxic than the other cationic lipoids, therefore they can be applied in lipofection and in drug delivery. However, a successful and effective use of these compounds requires detailed information of their mechanism of action, which is probably highly complex and multi-stages. However, the first barrier in the way to cell and thus the first side of action of these compounds is the cellular membrane. The aim of this work was to investigate the effect of one cationic lipoid, namely 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine (EPOPC) on model POPC/SM/Chol = 1:1:1 membranes. The experiments were performed on monolayer and bilayer systems and they involved the surface pressure measurements, Brewster angle microscopy studies, dynamic light scattering and zeta potential measurements and the experiments with the surfactant solution and steady-state fluorescence anisotropy of DPH and TMA-DPH. Moreover, to perform the studies systematically also the properties of the binary (POPC/EPOPC, SM/EPOPC, Chol/EPOPC) and ternary (POPC/Chol/EPOPC, SM/Chol/EPOPC) model systems were investigated. The obtained results indicated that even low concentration of EPOPC alters properties and organization of model membranes. Namely, EPOPC makes the interactions in model membrane weaker and increases fluidity and permeability of the lipid system. Finally, based on these data it can be proposed that the mechanism of action of EPOPC in lipofection/drug delivery involves the modifications in membrane organization, which facilitates the incorporation of drug or other material into the cell.
Topics: Cations; Cell Membrane Permeability; Cholesterol; Drug Delivery Systems; Membrane Fluidity; Membrane Lipids; Membranes, Artificial; Phosphatidylcholines; Sphingomyelins
PubMed: 31676373
DOI: 10.1016/j.bbamem.2019.183088