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The Journal of Membrane Biology Jun 2022The antineoplastic drug Docetaxel is a second generation taxane which is used against a great variety of cancers. The drug is highly lipophilic and produces a great...
The antineoplastic drug Docetaxel is a second generation taxane which is used against a great variety of cancers. The drug is highly lipophilic and produces a great array of severe toxic effects that limit its therapeutic effectiveness. The study of the interaction between Docetaxel and membranes is very scarce, however, it is required in order to get clues in relation with its function, mechanism of toxicity and possibilities of new formulations. Using phosphatidylcholine biomimetic membranes, we examine the interaction of Docetaxel with the phospholipid bilayer combining an experimental study, employing a series of biophysical techniques like Differential Scanning Calorimetry, X-Ray Diffraction and Infrared Spectroscopy, and a Molecular Dynamics simulation. Our experimental results indicated that Docetaxel incorporated into DPPC bilayer perturbing the gel to liquid crystalline phase transition and giving rise to immiscibility when the amount of the drug is increased. The drug promotes the gel ripple phase, increasing the bilayer thickness in the fluid phase, and is also able to alter the hydrogen-bonding interactions in the interfacial region of the bilayer producing a dehydration effect. The results from computational simulation agree with the experimental ones and located the Docetaxel molecule forming small clusters in the region of the carbon 8 of the acyl chain palisade overlapping with the carbonyl region of the phospholipid. Our results support the idea that the anticancer drug is embedded into the phospholipid bilayer to a limited amount and produces structural perturbations which might affect the function of the membrane.
Topics: 1,2-Dipalmitoylphosphatidylcholine; Calorimetry, Differential Scanning; Docetaxel; Lipid Bilayers; Membranes; Phosphatidylcholines; Phospholipids
PubMed: 35175383
DOI: 10.1007/s00232-022-00219-z -
The Analyst Oct 2022Characterization of glycerophospholipid isomers is of significant importance as they play different roles in physiological and pathological processes. In this work, we...
Characterization of glycerophospholipid isomers is of significant importance as they play different roles in physiological and pathological processes. In this work, we present a novel and bifunctional derivatization method utilizing Mn(II)-catalyzed epoxidation to simultaneously identify carbon-carbon double bond (CC bond)- and stereonumbering ()-positional isomers of phosphatidylcholine. Mn(II) coordinates with picolinic acid and catalyzes epoxidation of unsaturated lipids by peracetic acid. Collision-induced dissociation (CID) of the epoxides generates diagnostic ions that can be used to locate CC bond positions. Meanwhile, CID of Mn(II) ion-lipid complexes produces characteristic ions for determination of positions. This bifunctional derivatization takes place in seconds, and the diagnostic ions produced in CID are clear and easy to interpret. Moreover, relative quantification of CC bond-and -positional isomers was achieved. The capability of this method in identifying lipids at multiple isomer levels was shown using lipid standards and lipid extracts from complex biological samples.
Topics: Glycerophospholipids; Peracetic Acid; Phosphatidylcholines; Ions; Epoxy Compounds; Carbon; Catalysis
PubMed: 36128870
DOI: 10.1039/d2an01174c -
International Journal of Molecular... Feb 2022Salt stress is a major adverse abiotic factor seriously affecting fruit tree growth and development. It ultimately lowers fruit quality and reduces yield....
Salt stress is a major adverse abiotic factor seriously affecting fruit tree growth and development. It ultimately lowers fruit quality and reduces yield. Phosphatidylcholine (PC) is an important cell membrane component that is critical for cell structure and membrane stability maintenance. In this study, we found that the addition of external PC sources significantly increased the tolerance of one-year-old peach trees, (L.) Batsch., to salt stress and attenuated their damage. The effect of exogenous application of 200 mg/L PC exerted the most significant positive effect. Its use caused seedling leaf stomatal opening, contributing to normal gas exchange. Moreover, beneficial effects were exerted also to the root system, which grew normally under salt stress. Meanwhile, phospholipase D activity in the cell was promoted. The production of phosphatidic acid (PA) was enhanced by increased decomposition of phospholipids; PA serves as a secondary messenger involved in plant biological process regulation and the reduction in the reactive oxygen species- and peroxide-induced damage caused by salt stress. The possible mechanism of action is via promoted plant osmotic regulation and tolerance to salt stress, reducing salt stress-induced injury to plants.
Topics: Cell Membrane; Gene Expression Regulation, Plant; Homeostasis; Phosphatidic Acids; Phosphatidylcholines; Salt Stress; Seedlings; Stress, Physiological
PubMed: 35269728
DOI: 10.3390/ijms23052585 -
Frontiers in Immunology 2022Chronic urticaria (CU) is a chronic inflammatory skin disease mainly mediated by mast cells. Lipids exert essential functions in biological processes; however, the role...
Chronic urticaria (CU) is a chronic inflammatory skin disease mainly mediated by mast cells. Lipids exert essential functions in biological processes; however, the role of lipids in CU remains unclear. Nontargeted lipidomics was performed to investigate the differential lipid profiles between CU patients and healthy control (HC) subjects. Functional validation studies were performed and including β-hexosaminidase release examination from mast cells and passive cutaneous anaphylaxis (PCA) mouse model. We detected dramatically altered glycerophospholipids in CU patients compared with HCs. Phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) were increased, while phosphatidylcholine (PC) was reduced in CU patients. The reduction in PC was related to a high weekly urticaria activity score (UAS7), while PS was positively associated with the dermatology life quality index (DLQI). We also identified the differential lipid profiles between chronic spontaneous urticaria (CSU), symptomatic dermographism (SD), and CSU coexist with SD. CU patients were classified into two subtypes (subtype 1 and subtype 2) based on consensus clustering of lipid profiling. Compared with patients in subtype 2, patients in subtype 1 had elevated levels of PC (18:0e/18:2) and PE (38:2), and lower urticaria control test (UCT) scores indicated worse clinical efficiency of secondary generation H1 antihistamines treatment. Importantly, we found that supplementation with PC could attenuate IgE-induced immune responses in mast cells. In general, We described the landscape of plasma lipid alterations in CU patients and provided novel insights into the role of PC in mast cells.
Topics: Animals; Chronic Disease; Chronic Urticaria; Humans; Lipidomics; Mice; Phosphatidylcholines; Urticaria
PubMed: 35967440
DOI: 10.3389/fimmu.2022.933312 -
The Journal of Membrane Biology Jun 2020The path to our modern understanding of the structure of the lipid bilayer membrane is a long one that can be traced from today perhaps as far back as Benjamin Franklin... (Review)
Review
The path to our modern understanding of the structure of the lipid bilayer membrane is a long one that can be traced from today perhaps as far back as Benjamin Franklin in the eighteenth century. Here, I provide a personal account of one of the important steps in that path, the description of the "Complete Structure" of a hydrated, fluid phase dioleoyl phosphatidylcholine bilayer by the joint refinement of neutron and X-ray diffraction data by Stephen White and his colleagues.
Topics: Chemical Phenomena; Lipid Bilayers; Models, Molecular; Molecular Conformation; Molecular Structure; Phosphatidylcholines; Structure-Activity Relationship; X-Ray Diffraction
PubMed: 32488366
DOI: 10.1007/s00232-020-00126-1 -
Microbiological Research Feb 2011The phospholipid class and fatty acid composition of Legionella bozemanae were determined using thin-layer chromatography, gas-liquid chromatography, and matrix-assisted...
The phospholipid class and fatty acid composition of Legionella bozemanae were determined using thin-layer chromatography, gas-liquid chromatography, and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Phosphatidylcholine, phosphatidylethanolamine, and diphosphatidylglycerol were the predominant phospholipids, while phosphatidyl-N-monomethylethanolamine, phosphatidylglycerol, and phosphatidyl-N,N-dimethylethanolamine were present at low concentrations. With the use of the LC/MS technique, PC16:0/15:0, PC17:/15:0, and PE16:1/15:0 were shown to be the dominant phospholipid constituents, which may be taxonomically significant. Two independent phosphatidylcholine synthesis pathways (the three-step methylation and the one-step CDP-choline pathway) were present and functional in L. bozemanae. In the genome of L. bozemanae, genes encoding two potential phosphatidylcholine forming enzymes, phospholipid N-methyl transferase (PmtA) and phosphatidylcholine synthase (Pcs), homologous to L. longbeachae, L. drancourtii, and L. pneumophila pmtA and pcs genes were identified. Genes pmtA and pcs from L. bozemanae were sequenced and analyzed on nucleotide and amino acid levels. Bacteria grown on an artificial medium with labelled choline synthesized phosphatidylcholine predominantly via the phosphatidylcholine synthase pathway, which indicates that L. bozemanae phosphatidylcholine, similarly as in other bacteria associated with eukaryotes, is an important determinant of host-microbe interactions.
Topics: Bacterial Proteins; Base Sequence; Blotting, Southern; Choline; Fatty Acids; Legionella; Lipids; Mass Spectrometry; Methyltransferases; Phosphatidylcholines; Phylogeny; Polymerase Chain Reaction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transferases (Other Substituted Phosphate Groups)
PubMed: 20338739
DOI: 10.1016/j.micres.2010.02.004 -
Diabetes Care Feb 2015
Observational Study
Topics: Diabetes Mellitus, Type 2; Diet; Feeding Behavior; Female; Humans; Male; Phosphatidylcholines; Risk Factors
PubMed: 25614692
DOI: 10.2337/dc14-2093 -
Psychiatria Danubina 2020Anorexia nervosa (AN) is a serious mental disorder with a high mortality rate and often a chronic course. In contrast to many other common mental disorders, there is no... (Review)
Review
BACKGROUND
Anorexia nervosa (AN) is a serious mental disorder with a high mortality rate and often a chronic course. In contrast to many other common mental disorders, there is no drug therapy approved for AN.
METHODS
We performed a narrative literature review to consider whether a choline-containing molecule, such as phosphatidylcholine (PC), with an omega (ω)-3 long chain polyunsaturated fatty acid (LCPUFA) could be a potential future medicinal treatment for AN.
RESULTS
Choline and LCPUFAs have individually shown benefit for mental health. Case series and pilot studies suggest ω-3 LCPUFAs may be effective in eating disorders. However, pharmacodynamic and pharmacokinetic considerations suggest a greater benefit from the combination of both components.
CONCLUSION
The combination of a choline-containing molecule with an ω-3 LCPUFA may be clinically effective and well tolerated. This idea is supported by the current literature on the role of inflammation, the microbiome, the gut-brain-axis, hormonal, neurotransmitter and intracellular signalling, and on the structure and fluidity of nerve cells membranes in patients with AN.
Topics: Anorexia Nervosa; Brain; Fatty Acids, Omega-3; Humans; Inflammation; Phosphatidylcholines
PubMed: 32303030
DOI: 10.24869/psyd.2020.55 -
Biophysical Journal Nov 2022Phospholipid bilayers are liquid-crystalline materials whose intermolecular interactions at mesoscopic length scales have key roles in the emergence of membrane physical...
Phospholipid bilayers are liquid-crystalline materials whose intermolecular interactions at mesoscopic length scales have key roles in the emergence of membrane physical properties. Here we investigated the combined effects of phospholipid polar headgroups and acyl chains on biophysical functions of membranes with solid-state H NMR spectroscopy. We compared the structural and dynamic properties of phosphatidylethanolamine and phosphatidylcholine with perdeuterated acyl chains in the solid-ordered (s) and liquid-disordered (l) phases. Our analysis of spectral lineshapes of 1,2-diperdeuteriopalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE-d) and 1,2-diperdeuteriopalmitoyl-sn-glycero-3-phosphocholine (DPPC-d) in the s (gel) phase indicated an all-trans rotating chain structure for both lipids. Greater segmental order parameters (S) were observed in the l (liquid-crystalline) phase for DPPE-d than for DPPC-d membranes, while their mixtures had intermediate values irrespective of the deuterated lipid type. Our results suggest the S profiles of the acyl chains are governed by methylation of the headgroups and are averaged over the entire system. Variations in the acyl chain molecular dynamics were further investigated by spin-lattice (R) and quadrupolar-order relaxation (R) measurements. The two acyl-perdeuterated lipids showed distinct differences in relaxation behavior as a function of the order parameter. The R rates had a square-law dependence on S, implying collective mesoscopic dynamics, with a higher bending rigidity for DPPE-d than for DPPC-d lipids. Remodeling of lipid average and dynamic properties by methylation of the headgroups thus provides a mechanism to control the actions of peptides and proteins in biomembranes.
Topics: Phospholipids; 1,2-Dipalmitoylphosphatidylcholine; Phosphatidylcholines; Magnetic Resonance Spectroscopy; Lipid Bilayers
PubMed: 36088534
DOI: 10.1016/j.bpj.2022.09.005 -
Scientific Reports Jan 2019In this study, novel phosphatidylcholines containing ibuprofen or naproxen moieties were synthesized in good yields and high purities. Under the given synthesis...
In this study, novel phosphatidylcholines containing ibuprofen or naproxen moieties were synthesized in good yields and high purities. Under the given synthesis conditions, the attached drug moieties racemized, which resulted in the formation of phospholipid diastereomers. The comperative studies of the cytotoxicity of ibuprofen, naproxen and their phosphatidylcholine derivatives against human promyelocytic leukemia HL-60, human colon carcinoma Caco-2, and porcine epithelial intestinal IPEC-J2 cells were carried out. The results of these studies indicated that phospholipids with NSAIDs at both sn-1 and sn-2 positions (15 and 16) were more toxic than ibuprofen or naproxen themselves, whereas 2-lysophosphatidylcholines (7 and 8) were less toxic against all tested cell lines. Phospholipids with NSAIDs at sn-1 and palmitic acid at sn-2 (9 and 10) were also less toxic against Caco-2 and normal cells (IPEC-J2).
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Caco-2 Cells; Cell Line; Cytotoxins; Epithelial Cells; Humans; Ibuprofen; Lysophosphatidylcholines; Naproxen; Palmitic Acid; Phosphatidylcholines; Phospholipids; Swine
PubMed: 30659229
DOI: 10.1038/s41598-018-36571-1