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Molecules (Basel, Switzerland) Jul 2023Phosphatidylcholine-specific phospholipase C (PC-PLC) is an enzyme that catalyzes the formation of the important secondary messengers phosphocholine and diacylglycerol... (Review)
Review
Phosphatidylcholine-specific phospholipase C (PC-PLC) is an enzyme that catalyzes the formation of the important secondary messengers phosphocholine and diacylglycerol (DAG) from phosphatidylcholine. Although PC-PLC has been linked to the progression of many pathological conditions, including cancer, atherosclerosis, inflammation and neuronal cell death, studies of PC-PLC on the protein level have been somewhat neglected with relatively scarce data. To date, the human gene expressing PC-PLC has not yet been found, and the only protein structure of PC-PLC that has been solved was from (PC-PLC). Nonetheless, there is evidence for PC-PLC activity as a human functional equivalent of its prokaryotic counterpart. Additionally, inhibitors of PC-PLC have been developed as potential therapeutic agents. The most notable classes include 2-aminohydroxamic acids, xanthates, ,'-hydroxyureas, phospholipid analogues, 1,4-oxazepines, pyrido[3,4-]indoles, morpholinobenzoic acids and univalent ions. However, many medicinal chemistry studies lack evidence for their cellular and in vivo effects, which hampers the progression of the inhibitors towards the clinic. This review outlines the pathological implications of PC-PLC and highlights current progress and future challenges in the development of PC-PLC inhibitors from the literature.
Topics: Humans; Type C Phospholipases; Phosphatidylcholines
PubMed: 37570610
DOI: 10.3390/molecules28155637 -
Respiratory Research Mar 2011Patients with adult respiratory distress syndrome (ARDS) and acute lung injury (ALI) have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B...
BACKGROUND
Patients with adult respiratory distress syndrome (ARDS) and acute lung injury (ALI) have low concentrations of disaturated-phosphatidylcholine and surfactant protein-B in bronchoalveolar lavage fluid. No information is available on their turnover.
OBJECTIVES
To analyze disaturated-phosphatidylcholine and surfactant protein-B turnover in patients with ARDS/ALI and in human adults with normal lungs (controls).
METHODS
2H2O as precursor of disaturated-phosphatidylcholine-palmitate and 113C-Leucine as precursor of surfactant protein-B were administered intravenously to 12 patients with ARDS/ALI and to 8 controls. Disaturated-phosphatidylcholine and surfactant protein-B were isolated from serial tracheal aspirates, and their fractional synthetic rate was derived from the 2H and 13C enrichment curves, obtained by gas chromatography mass spectrometry. Disaturated-phosphatidylcholine, surfactant protein-B, and protein concentrations in tracheal aspirates were also measured.
RESULTS
1) Surfactant protein-B turned over at faster rate than disaturated-phosphatidylcholine both in ARDS/ALI patients and in controls. 2) In patients with ARDS/ALI the fractional synthesis rate of disaturated-phosphatidylcholine was 3.1 times higher than in controls (p < 0.01), while the fractional synthesis rate of surfactant protein-B was not different. 3) In ARDS/ALI patients the concentrations of disaturated-phosphatidylcholine and surfactant protein-B in tracheal aspirates were markedly and significantly reduced (17% and 40% of the control values respectively).
CONCLUSIONS
1) Disaturated-phosphatidylcholine and surfactant protein-B have a different turnover both in healthy and diseased lungs. 2) In ARDS/ALI the synthesis of these two surfactant components may be differently regulated.
Topics: Acute Lung Injury; Adult; Biomarkers; Bronchoalveolar Lavage Fluid; Case-Control Studies; Female; Humans; Italy; Kinetics; Male; Middle Aged; Phosphatidylcholines; Pulmonary Surfactant-Associated Protein B; Young Adult
PubMed: 21429235
DOI: 10.1186/1465-9921-12-36 -
Journal of Oleo Science Dec 2021The antiadipogenic activity of conjugated linoleic acids (CLA) in the form of phosphatidylcholine-bound (CLA-PC) or free fatty acids (FFA; CLA-FFA) was evaluated using... (Comparative Study)
Comparative Study
The antiadipogenic activity of conjugated linoleic acids (CLA) in the form of phosphatidylcholine-bound (CLA-PC) or free fatty acids (FFA; CLA-FFA) was evaluated using 3T3-L1 adipocytes. Phosphatidylcholine from soya (soy-PC) was used as the comparison of PC form. Both the lipid accumulation and activity of glycerol-3-phosphate dehydrogenase were measured to determine lipogenesis, whereas the glycerol content was measured to evaluate lipolysis. The CLA uptake also measured to find out the utilization of CLA by the cells. As a results, lipid accumulation in 3T3-L1 adipocytes was inhibited in a dose-dependent manner following treatment with CLA-PC (50-400 μM). Both CLA-PC and soy-PC significantly suppressed lipid accumulation compared with CLA-FFA, even though the amount of CLA in CLA-PC was a half than CLA-FFA. The CLA uptake of PC form was superior to FFA form, however, no difference was noted between CLA-PC and soy-PC. These forms exerted their antiadipogenic activity via the suppression of lipogenesis, and not by increasing lipolysis. Short-term treatment, especially in the middle stage of differentiation, was more effective than long-term treatment; especially for CLA-FFA. The antiadipogenic effect of CLA-PC was partially attributed to the chemical structure of the PC molecule. These results provide important information for the utilization of physiologically functional fatty acids and particularly CLA in the food and medical fields.
Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Fatty Acids, Nonesterified; Linoleic Acids, Conjugated; Lipogenesis; Mice; Phosphatidylcholines; Glycine max; Structure-Activity Relationship
PubMed: 34759111
DOI: 10.5650/jos.ess21180 -
Biochimica Et Biophysica Acta Nov 1998Pulmonary surfactant is composed of approx. 90% lipids and 10% protein. This review article focusses on the lipid components of surfactant. The first sections will... (Review)
Review
Pulmonary surfactant is composed of approx. 90% lipids and 10% protein. This review article focusses on the lipid components of surfactant. The first sections will describe the lipid composition of mammalian surfactant and the techniques that have been utilized to study the involvement of these lipids in reducing the surface tension at an air-liquid interface, the main function of pulmonary surfactant. Subsequently, the roles of specific lipids in surfactant will be discussed. For the two main surfactant phospholipids, phosphatidylcholine and phosphatidylglycerol, specific contributions to the overall surface tension reducing properties of surfactant have been indicated. In contrast, the role of the minor phospholipid components and the neutral lipid fraction of surfactant is less clear and requires further study. Recent technical advances, such as fluorescent microscopic techniques, hold great potential for expanding our knowledge of how surfactant lipids, including some of the minor components, function. Interesting information regarding surfactant lipids has also been obtained in studies evaluating the surfactant system in non-mammalian species. In certain non-mammalian species (and at least one marsupial), surfactant lipid composition, most notably disaturated phosphatidylcholine and cholesterol, changes drastically under different conditions such as an alteration in body temperature. The impact of these changes on surfactant function provide insight into the function of these lipids, not only in non-mammalian lungs but also in the surfactant from mammalian species.
Topics: Animals; Lipids; Lung; Phosphatidylcholines; Phosphatidylglycerols; Phosphatidylinositols; Physiology; Pulmonary Surfactants; Surface Tension; Vertebrates
PubMed: 9813256
DOI: 10.1016/s0925-4439(98)00061-1 -
Journal of Oleo Science Jun 2022Eggs are nutritious and cheap and easily available. Egg yolk is one of the sources of phosphatidylcholine (PC) and phosphatidylethanolamine (PE). PC and PE have good...
Eggs are nutritious and cheap and easily available. Egg yolk is one of the sources of phosphatidylcholine (PC) and phosphatidylethanolamine (PE). PC and PE have good emulsifying properties, and they are widely used and in high demand for pharmaceutical, feed and cosmetic applications. Red cordyceps egg yolk powder (RCEYP) was selected as the raw material to obtain high content of PC and PE by ethanol extraction and low temperature cryoprecipitation in n-hexane-acetone system (HAS), in which the process conditions of PC and PE extraction by HAS process were optimized. The phospholipids were quantified by high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD). The effects of freezing time, material-liquid ratio, acetone washing times, solvent ratio of n-hexane to acetone and freezing temperature on the PC and PE contents and the phospholipid yield were investigated. The optimal conditions for the extraction of PC and PE from RCEYP by HAS were determined by Box-Behnken design (BBD) as follows: the solvent ratio of n-hexane to acetone was 1:6, the freezing time was 11.31 h, and the freezing temperature was -19°C. The total content of (PC+PE) in the phospholipids precipitated under these conditions amounted to 96.16%, of which 81.12% was PC and 15.04% was PE.
Topics: Acetone; Hexanes; Lecithins; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids; Solvents
PubMed: 35584957
DOI: 10.5650/jos.ess22011 -
Journal of Cosmetic Dermatology Oct 2022
Topics: Humans; Mesotherapy; Phosphatidylcholines; Adipose Tissue; Injections, Subcutaneous
PubMed: 35094461
DOI: 10.1111/jocd.14809 -
Clinical Pharmacology and Therapeutics Apr 1982In six normal subjects we investigated the effects of oral phosphatidylcholine (lecithin) on the concentrations of plasma choline, erythrocyte choline, and...
In six normal subjects we investigated the effects of oral phosphatidylcholine (lecithin) on the concentrations of plasma choline, erythrocyte choline, and choline-containing lipids. Plasma choline levels rose 1 hr after treatment and remained elevated for 8 hr, with peaks at 3 and 4 hr after phosphatidylcholine. Erythrocyte choline levels also rose, although the rise was slightly delayed relative to plasma choline. There was no change in the plasma choline-containing lipid concentration. These results demonstrate that, in normal subjects, oral phosphatidylcholine indices prolonged rises in plasma and erythrocyte choline concentrations and is therefore useful when such effects are desired.
Topics: Choline; Erythrocytes; Humans; Lipids; Phosphatidylcholines
PubMed: 7060329
DOI: 10.1038/clpt.1982.64 -
Journal of Lipid Research Jan 2018DHA is important for fetal neurodevelopment. During pregnancy, maternal plasma DHA increases, but the mechanism is not fully understood. Using rats fed a fixed-formula...
DHA is important for fetal neurodevelopment. During pregnancy, maternal plasma DHA increases, but the mechanism is not fully understood. Using rats fed a fixed-formula diet (DHA as 0.07% total energy), plasma and liver were collected for fatty acid profiling before pregnancy, at 15 and 20 days of pregnancy, and 7 days postpartum. Phosphatidylethanolamine methyltransferase (PEMT) and enzymes involved in PUFA synthesis were examined in liver. Ad hoc transcriptomic and lipidomic analyses were also performed. With pregnancy, DHA increased in liver and plasma lipids, with a large increase in plasma DHA between day 15 and day 20 that was mainly attributed to an increase in 16:0/DHA phosphatidylcholine (PC) in liver (2.6-fold) and plasma (3.9-fold). Increased protein levels of Δ6 desaturase (FADS2) and PEMT at day 20 and increased expression and PEMT activity at day 15 suggest that during pregnancy, both DHA synthesis and 16:0/DHA PC synthesis are upregulated. Transcriptomic analysis revealed minor changes in the expression of genes related to phospholipid synthesis, but little insight on DHA metabolism. Hepatic PEMT appears to be the mechanism for increased plasma 16:0/DHA PC, which is supported by increased DHA biosynthesis based on increased FADS2 protein levels.
Topics: Animals; Female; Linoleoyl-CoA Desaturase; Phosphatidylcholines; Phosphatidylethanolamine N-Methyltransferase; Pregnancy; Rats; Rats, Sprague-Dawley
PubMed: 29167412
DOI: 10.1194/jlr.M080309 -
PloS One 2014Milk and dairy products are an important source of choline, a nutrient essential for human health. Infant formula derived from bovine milk contains a number of metabolic...
Milk and dairy products are an important source of choline, a nutrient essential for human health. Infant formula derived from bovine milk contains a number of metabolic forms of choline, all contribute to the growth and development of the newborn. At present, little is known about the factors that influence the concentrations of choline metabolites in milk. The objectives of this study were to characterize and then evaluate associations for choline and its metabolites in blood and milk through the first 37 weeks of lactation in the dairy cow. Milk and blood samples from twelve Holstein cows were collected in early, mid and late lactation and analyzed for acetylcholine, free choline, betaine, glycerophosphocholine, lysophosphatidylcholine, phosphatidylcholine, phosphocholine and sphingomyelin using hydrophilic interaction liquid chromatography-tandem mass spectrometry, and quantified using stable isotope-labeled internal standards. Total choline concentration in plasma, which was almost entirely phosphatidylcholine, increased 10-times from early to late lactation (1305 to 13,535 µmol/L). In milk, phosphocholine was the main metabolite in early lactation (492 µmol/L), which is a similar concentration to that found in human milk, however, phosphocholine concentration decreased exponentially through lactation to 43 µmol/L in late lactation. In contrast, phosphatidylcholine was the main metabolite in mid and late lactation (188 µmol/L and 659 µmol/L, respectively), with the increase through lactation positively correlated with phosphatidylcholine in plasma (R2 = 0.78). Unlike previously reported with human milk we found no correlation between plasma free choline concentration and milk choline metabolites. The changes in pattern of phosphocholine and phosphatidylcholine in milk through lactation observed in the bovine suggests that it is possible to manufacture infant formula that more closely matches these metabolites profile in human milk.
Topics: Animals; Cattle; Choline; Female; Humans; Lactation; Milk; Phosphatidylcholines
PubMed: 25157578
DOI: 10.1371/journal.pone.0103412 -
Biophysical Journal Nov 2021A mesoscopic model with molecular resolution is presented for dipalmitoyl phosphatidylcholine (DPPC) and palmitoyl oleoyl phosphatidylcholine (POPC) monolayer...
A mesoscopic model with molecular resolution is presented for dipalmitoyl phosphatidylcholine (DPPC) and palmitoyl oleoyl phosphatidylcholine (POPC) monolayer simulations at the air-water interface using many-body dissipative particle dynamics (MDPD). The parameterization scheme is rigorously based on reproducing the physical properties of water and alkane and the interfacial property of the phospholipid monolayer by comparison with experimental results. Using much less computing cost, these MDPD simulations yield a similar surface pressure-area isotherm as well as similar pressure-related morphologies as all-atom simulations and experiments. Moreover, the compressibility modulus, order parameter of lipid tails, and thickness of the phospholipid monolayer are quantitatively in line with the all-atom simulations and experiments. This model also captures the sensitive changes in the pressure-area isotherms of mixed DPPC/POPC monolayers with altered mixing ratios, indicating that the model is promising for applications with complex natural phospholipid monolayers. These results demonstrate a significant improvement of quantitative phospholipid monolayer simulations over previous coarse-grained models.
Topics: 1,2-Dipalmitoylphosphatidylcholine; Phosphatidylcholines; Phospholipids; Pulmonary Surfactants; Surface Properties; Water
PubMed: 34562445
DOI: 10.1016/j.bpj.2021.09.031