Phosphatidylcholine Content Research Articles

Oncogene Amplification in Growth Factor Signaling Pathways Renders Cancers Dependent on Membrane Lipid Remodeling

Advances in DNA sequencing technologies have reshaped our understanding of the molecular basis of cancer, providing a precise genomic view of tumors. Complementary biochemical and biophysical perspectives of cancer point toward profound shifts in nutrient uptake and utilization that propel tumor growth and major changes in the structure of the plasma membrane of tumor cells. The molecular mechanisms that bridge these fundamental aspects of tumor biology remain poorly understood. Here, we show that the lysophosphatidylcholine acyltransferase LPCAT1 functionally links specific genetic alterations in cancer with aberrant metabolism and plasma membrane remodeling to drive tumor growth. Growth factor receptor-driven cancers are found to depend on LPCAT1 to shape plasma membrane composition through enhanced saturated phosphatidylcholine content that is, in turn, required for the transduction of oncogenic signals. These results point to a genotype-informed strategy that prioritizes lipid remodeling pathways as therapeutic targets for diverse cancers.

Total liver phosphatidylcholine content associates with non-alcoholic steatohepatitis and glycine N-methyltransferase expression.

Alterations in liver phosphatidylcholine (PC) metabolism have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Although genetic variation in the phosphatidylethanolamine N-methyltransferase (PEMT) enzyme synthesizing PC has been associated with disease, the functional mechanism linking PC metabolism to the pathogenesis of non-alcoholic steatohepatitis (NASH) remains unclear. Serum PC levels and liver PC contents were measured using proton nuclear magnetic resonance (NMR) spectroscopy in 169 obese individuals [age 46.6±10 (mean±SD) years, BMI 43.3±6kg/m2 , 53 men and 116 women] with histological assessment of NAFLD; 106 of these had a distinct liver phenotype. All subjects were genotyped for PEMT rs7946 and liver mRNA expression of PEMT and glycine N-methyltransferase (GNMT) was analysed. Liver PC content was lower in those with NASH (P=1.8x10-6 ) while serum PC levels did not differ between individuals with NASH and normal liver (P=0.591). Interestingly, serum and liver PC did not correlate (rs =-0.047, P=0.557). Serum PC and serum cholesterol levels correlated strongly (rs =0.866, P=7.1x10-49 ), while liver PC content did not correlate with serum cholesterol (rs =0.065, P=0.413). Neither PEMT V175M genotype nor PEMT expression explained the association between liver PC content and NASH. Instead, liver GNMT mRNA expression was decreased in those with NASH (P=3.8x10-4 ) and correlated with liver PC content (rs =0.265, P=0.001). Decreased liver PC content in individuals with the NASH is independent of PEMT V175M genotype and could be partly linked to decreased GNMT expression.

Interfacial structure of 70% fish oil-in-water emulsions stabilized with combinations of sodium caseinate and phosphatidylcholine

We report on the structural evaluation of high fat fish oil-in-water emulsions emulsified with sodium caseinate (CAS) and phosphatidylcholine (PC). The microemulsions contained 70% (w/w) fish oil with 1.05–1.4% (w/w) CAS and 0.4–1.75% (w/w) PC and were studied by the combination of light scattering together with small-angle X-ray and neutron scattering (SAXS/SANS). Aqueous CAS forms aggregates having a denser core of about 100 kDa and less dense shell about 400 kDa with the hard sphere diameter of 20.4 nm. PC appears as multilayers whose coherence length spans from 40 to 100 nm. PC monolayer separates oil and water phases. Moreover, 80% CAS particles are loosely bound to the interface but are not forming continuous coverage. The distance between aggregated CAS particles in microemulsion is increased compared to CAS aggregates in pure CAS-in-water system. PC multilayers become larger in the presence of oil-water interface compared to the pure PC mixtures. Bilayers become larger with increasing PC concentration. This study forms a structural base for the combination of CAS and PC emulsifiers forming a well-defined thin and dense PC layer together with thick but less dense CAS layer, which is assumed to explain its better oxidative stability compared to single emulsifiers.

Metabolic Disturbances Identified in Plasma Samples from ST-Segment Elevation Myocardial Infarction Patients.

ST-segment elevation myocardial infarction (STEMI) is the most severe form of myocardial infarction (MI) and the main contributor to morbidity and mortality caused by MI worldwide. Frequently, STEMI is caused by complete and persistent occlusion of a coronary artery by a blood clot, which promotes heart damage. STEMI impairment triggers changes in gene transcription, protein expression, and metabolite concentrations, which grants a biosignature to the heart dysfunction. There is a major interest in identifying novel biomarkers that could improve the diagnosis of STEMI. In this study, the phenotypic characterization of STEMI patients (n = 15) and healthy individuals (n = 19) was performed, using a target metabolomics approach. Plasma samples were analyzed by UPLC-MS/MS (ultra-high-performance liquid chromatography-tandem mass spectrometry) and FIA-MS (MS-based flow injection analysis). The goal was to identify novel plasma biomarkers and metabolic signatures underlying STEMI. Concentrations of phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, and biogenic amines were altered in STEMI patients in relation to healthy subjects. Also, after multivariate analysis, it was possible to identify alterations in the glycerophospholipids, alpha-linolenic acid, and sphingolipid metabolisms in STEMI patients.

Content and Composition of Lipids and Their Fatty Acids in Needles of Pinus sylvestris L. and Picea obovata Ledeb. upon Cold Hardening in the Cryolithozone of Yakutia

The composition of lipids and fatty acids (FAs) and changes in their content in needles of summer- and autumn-vegetating conifer trees growing in the cryolithozone of Yakutia have been studied by thin-layer and gas-liquid chromatography–mass spectrometry. A comparative analysis of the content of total lipids (TL) and phospholipids (PL) has been carried out, and the FA composition of TL in needles of Pinus sylvestris L. and Picea obovata Ledeb. has been determined for summer and autumn periods. In the course of adaptation to low autumn temperatures of the Yakutian cryolithozone, the TL content in needles of P. sylvestris and P. obovata significantly (by 30%) increased compared to the summer season. During this period, the phosphatidylcholine content in needles of both species also increased from 13.8 to 31 mg/g dry wt. For both species, the FA lipid composition of needles included a high content of species-specific unsaturated polymethylene-interrupted fatty acids (Δ5-UPIFA). Increase in the content of TL, PL, total FA, and Δ5-UPIFA observed during a temperature drop significantly exceeds that in plants of these species growing in other parts of Siberia. This fact is probably caused by features of low-temperature adaptation of plants in permafrost ecosystems of Yakutia.

Abstract 3601: Dietary phosphatidylcholine depletion reduces tumor development independent of autotaxin inhibition in hyperlipidemic mouse models of breast cancer

Abstract Lysophosphatidic acid (LPA) is a pleiotropic growth-factor lysophospholipid that promotes cancer cell survival, growth, migration, invasion, metastasis, and resistance to chemotherapy and radiotherapy. The main precursor for LPA, lysophosphatidylcholine (LPC) is derived majorly from the highly abundant phosphatidylcholine (PC). Hydrolysis of LPC to the circulating LPA is catalyzed by the enzyme autotaxin (ATX), a secreted lysophospholipase D. We investigated the effects of altering dietary intake of PC and pharmacological inhibition of ATX on breast cancer development in mice. To formulate diets with defined PC levels we used tandem mass spectrometry to measure the concentration of PC in various components of fat used to manufacture rodent diets. We determined that casein is the main source of PC when present in rodent diets. High fat diets (60% kcal fat) were formulated with casein (high PC) or amino acids in place of casein (low PC). To study the effects of these diets on breast cancer development, six-week old female C57Bl6 low density lipoprotein receptor knockout mice (LDLr-/-) were fed high fat diets for 12 weeks. Subsequently, E0771 syngeneic mammary cells were injected into the inguinal mammary fat pads of mice fed continuously on high fat diets. At the time of tumor cell inoculation, the animals were divided into groups to either receive daily dosage of a novel potent ATX inhibitor or vehicle control. Primary tumor growth was monitored using orthogonal caliper measurements and tumor volumes estimated from width2 × length/2. The number of metastatic nodules in the lungs were counted after staining with India ink. In high fat diet mouse models of breast cancer we observed that feeding mice with diets in which casein is replaced with amino acids decreases primary tumor growth. Contrary to our expectation, treatment with a potent ATX inhibitor resulted in no significant effect on primary tumor growth and an increased number of metastatic nodules compared with vehicle-treated mice. Moreover, treatment with the ATX inhibitor reversed the beneficial effects of casein replacement and instead resulted in enhanced tumor growth and metastasis. These studies suggest that dietary casein promotes primary tumor growth in the hyperlipidemic E0771 models of cancer and that targeting ATX inhibition is not efficacious in these models. Our results show that under certain hyperlipidemic conditions consumption of dietary casein can promote primary tumor growth. We also provide evidence emphasizing the need for further investigation in ascertaining the impact and utility of ATX inhibitors in breast cancer treatment. Citation Format: Fredrick O. Onono, Ebubechi Adindu, Baoxiang Yan, Sony Soman, Courtney Hammill, Andrew J. Morris. Dietary phosphatidylcholine depletion reduces tumor development independent of autotaxin inhibition in hyperlipidemic mouse models of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3601.

Effects of hot air drying process on lipid quality of whelks Neptunea arthritica cumingi Crosse and Neverita didyma.

Whelks Neptunea arthritica cumingi Crosse and Neverita didyma were processed by hot air drying and changes of thei lipids and the mechanism involved were evaluated by analyzing peroxide value, thiobarbituric acid-reactive substances, total oxidation value, fatty acid composition, activities of lipases and lipoxygenase (LOX), as well as contents of triacylglycerol (TAG), free fatty acid (FFA), phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The processing significantly decreased the contents of PC, PE and TAG but increased the content of FFA. The presence of acid lipase and phospholipase in whelk tissues and their activity preservation during processing suggest that the enzymes may help hydrolyze lipids. By contrast, the reduction of PC, PE and TAG was more pronounced than the increase in FFA in whelk tissues upon processing, indicating the oxidative degradation of FFA. LOX may play a role in lipid oxidation due to the stability of the starting components during processing.

Cholinergic nervous system and glaucoma: From basic science to clinical applications.

The cholinergic system has a crucial role to play in visual function. Although cholinergic drugs have been a focus of attention as glaucoma medications for reducing eye pressure, little is known about the potential modality for neuronal survival and/or enhancement in visual impairments. Citicoline, a naturally occurring compound and FDA approved dietary supplement, is a nootropic agent that is recently demonstrated to be effective in ameliorating ischemic stroke, traumatic brain injury, Parkinson's disease, Alzheimer's disease, cerebrovascular diseases, memory disorders and attention-deficit/hyperactivity disorder in both humans and animal models. The mechanisms of its action appear to be multifarious including (i) preservation of cardiolipin, sphingomyelin, and arachidonic acid contents of phosphatidylcholine and phosphatidylethanolamine, (ii) restoration of phosphatidylcholine, (iii) stimulation of glutathione synthesis, (iv) lowering glutamate concentrations and preventing glutamate excitotoxicity, (v) rescuing mitochondrial function thereby preventing oxidative damage and onset of neuronal apoptosis, (vi) synthesis of myelin leading to improvement in neuronal membrane integrity, (vii) improving acetylcholine synthesis and thereby reducing the effects of mental stress and (viii) preventing endothelial dysfunction. Such effects have vouched for citicoline as a neuroprotective, neurorestorative and neuroregenerative agent. Retinal ganglion cells are neurons with long myelinated axons which provide a strong rationale for citicoline use in visual pathway disorders. Since glaucoma is a form of neurodegeneration involving retinal ganglion cells, citicoline may help ameliorate glaucomatous damages in multiple facets. Additionally, trans-synaptic degeneration has been identified in humans and experimental models of glaucoma suggesting the cholinergic system as a new brain target for glaucoma management and therapy.

Maternal glyphosate-based herbicide exposure alters antioxidant-related genes in the brain and serum metabolites of male rat offspring

In response to the rapid development of genetically engineered glyphosate-tolerant crops, the use of glyphosate-based herbicides (GBHs), in agriculture, has increased substantially. Currently, it is estimated that 747 million kg of GBHs are applied per year. Although several epidemiological studies have demonstrated that there are health risks associated with GBH exposure, the effects these chemicals have on the oxidative and inflammatory response in the brain are still unclear. In fact, alterations in these processes could contribute to the development of neurological diseases, such as Alzheimer’s disease and autism spectrum disorders. The present study exposed pregnant rats to GBH and evaluated changes in the expression of genes related to oxidnte defense and inflammation response and monitored the serum metabolome in the adult male offspring. Pregnant Wistar rats were administered distilled water or Roundup®, at either 5 and 50 mg/kg/day, (p.o.) from gestational day (GD) 18 to postnatal day (PND) 5. There was a significant increase in the gene expression levels of Neuroglobin (Ngb – oxygen storage and tissue protection) (105%, p = 0.031), Glutathione Peroxidase 1 (Gpx1 – oxidative stress) (95%, p = 0.005), Prostaglandin-Endoperoxidase Synthase 1 (Ptgs1 - inflammation) (109%, p = 0.033) and Hypoxia inducible factor 1 subunit alpha (Hif1α – oxygen sensor) (73%, p = 0.017), in the cerebellum of PND90 rats perinatally exposed to 50 mg GBH/kg/day. Moreover, both GBH-exposed groups displayed a significant decrease in the expression of Catalase (Cat – oxidative stress) (49%, p = 0.003; and 31% p = 0.050, respectively) expression, in the cortex. Serum metabolites analyses, from the same animals of each group, demonstrated that there were significant changes in the concentrations of lysophosphatidylcholine and phosphatidylcholine, which have been associated with neurodegenerative diseases. The results of the present study suggest GBH exposure during pregnancy alters the expression of genes associated with oxidant defense, inflammation and lipid metabolism. It is plausible that maternal GBH exposure could have lasting neuronal effects on the offspring later in life.

Characterization of Bulk Phosphatidylcholine Compositions in Human Plasma Using Side-Chain Resolving Lipidomics.

Kit-based assays, such as AbsoluteIDQTM p150, are widely used in large cohort studies and provide a standardized method to quantify blood concentrations of phosphatidylcholines (PCs). Many disease-relevant associations of PCs were reported using this method. However, their interpretation is hampered by lack of functionally-relevant information on the detailed fatty acid side-chain compositions as only the total number of carbon atoms and double bonds is identified by the kit. To enable more substantiated interpretations, we characterized these PC sums using the side-chain resolving LipidyzerTM platform, analyzing 223 samples in parallel to the AbsoluteIDQTM. Combining these datasets, we estimated the quantitative composition of PC sums and subsequently tested their replication in an independent cohort. We identified major constituents of 28 PC sums, revealing also various unexpected compositions. As an example, PC 16:0_22:5 accounted for more than 50% of the PC sum with in total 38 carbon atoms and 5 double bonds (PC aa 38:5). For 13 PC sums, we found relatively high abundances of odd-chain fatty acids. In conclusion, our study provides insights in PC compositions in human plasma, facilitating interpretation of existing epidemiological data sets and potentially enabling imputation of PC compositions for future meta-analyses of lipidomics data.

Effects of abomasal infusions of fatty acids and one-carbon donors on hepatic ceramide and phosphatidylcholine in lactating Holstein dairy cows

Our objectives were to (1) determine whether the abomasal infusion of behenic acid (C22:0) elevated hepatic ceramide relative to palmitic acid (C16:0) or docosahexaenoic acid (C22:6n-3) infusion; (2) assess whether the abomasal infusion of choline chloride or l-serine elevated hepatic phosphatidylcholine (PC) in cows abomasally infused with C16:0; and (3) characterize the PC lipidome in cows abomasally infused with C22:6n-3, relative to C16:0 or C22:0 infusion. In a 5 × 5 Latin square design, 5 rumen-cannulated Holstein cows (214 ± 4.9 DIM; 3.2 ± 1.1 parity) were enrolled in a study with 6-d periods. Abomasal infusates consisted of (1) palmitic acid (PA; 98% C16:0); (2) PA + choline chloride (PA+C; 50 g/d choline chloride); (3) PA + l-serine (PA+S; 170 g/d l-serine); (4) behenic acid (BA; 92% C22:0); and (5) an algal oil rich in docosahexaenoic acid (DHA; 44% C22:6n-3). Emulsion infusates provided 301 g/d of total fatty acids containing a minimum of 40 g/d of C16:0. Cows were fed a corn silage-based diet. Milk was collected on d -2, -1, 5, and 6. Blood was collected and liver biopsied on d 6 of each period. Although we did not detect differences in milk yield, milk fat yield and content were lower in cows infused with DHA relative to PA. Plasma triacylglycerol concentrations were lower with DHA treatment relative to PA or BA. Cows infused with DHA had lower plasma insulin concentrations relative to cows infused with PA only. For objective 1, hepatic ceramide-d18:2/22:0 was highest in cows infused with BA relative to other treatments. For objective 2, plasma free choline concentrations were greater in PA+C cows relative to PA; however, we did not observe this effect with PA+S. Plasma total PC concentrations were similar for all treatments. Regarding the hepatic lipidome, a total of 18 hepatic PC were higher (e.g., PC-16:1/18:2) and 25 PC were lower (e.g., PC-16:0/22:6) with PA+C infusion relative to PA. In addition, 17 PC were higher (e.g., PC-20:3/22:5) and 21 PC were lower (e.g., PC-18:0/22:6) with PA+S infusion relative to PA. For objective 3, hepatic concentrations of many individual saturated PC (e.g., PC-18:0/15:0) were lower with DHA relative to other treatments. Hepatic concentrations of highly unsaturated PC with very-long-chain fatty acids (e.g., PC-14:0/22:6) were higher in DHA-infused cows relative to PA, PA+C, PA+S, or BA. The abomasal infusion of emulsions containing palmitic acid, palmitic acid with choline chloride or serine, behenic acid, or docosahexaenoic acid influence the hepatic ceramide and PC profiles of lactating cows.

Mitochondrial membranes in cardiac muscle from Antarctic notothenioid fishes vary in phospholipid composition and membrane fluidity.

Antarctic notothenioid fishes are highly stenothermal, yet their tolerance for warming is species-dependent. Because a body of literature points to the loss of cardiac function as underlying thermal limits in ectothermic animals, we investigated potential relationships among properties of ventricular mitochondrial membranes in notothenioids with known differences in both cardiac mitochondrial metabolism and organismal thermal tolerance. Fluidity of mitochondrial membranes was quantified by fluorescence depolarization for the white-blooded Chaenocephalus aceratus and the red-blooded Notothenia coriiceps. In these same membranes, lipid compositions and products of lipid peroxidation, the latter of which can disrupt membrane order, were analyzed in both species and in a second icefish, Pseudochaenichthys georgianus. Mitochondrial membranes from C. aceratus were significantly more fluid than those of the more thermotolerant species N. coriiceps (P < .0001). Consistent with this, ratios of total phosphatidylethanolamine (PE) to total phosphatidylcholine (PC) were lower in membranes from both species of icefishes, compared to those of N. coriiceps (P < .05). However, membranes of N. coriiceps displayed a greater unsaturation index (P < .0001). No differences among species were found in membrane products of lipid peroxidation. With rising temperatures, greater contents of PC in mitochondrial membranes from ventricles of icefishes are likely to promote membrane hyperfluidization at a lower temperature than for cardiac mitochondrial membranes from the red-blooded notothenioid. We propose that physical and chemical properties of the mitochondrial membranes may contribute to some of the observed differences in thermal sensitivity of physiological function among these species.

Formulation development of ethosomes containing indomethacin for transdermal delivery

2 Ethosomes containing indomethacin (8 mg/mL) were prepared with various concentrations of soybean phosphatidylcholine (SPC), ethanol and with different dispersion media and additives. The ethosomes with good colloidal appearance were obtained in the media containing 10%-30% ethanol in pH 7.4 phosphate buffer. The properties of ethosomes, including physical appearances, size, and entrapment efficiency (EE), were examined and discussed concerning their constituents. Notably significant decreases in vesicular size were observed at 20% ethanol (2% and 4% SPC) and 30% ethanol (6% SPC). The EE was varied relating to the vesicular size and concentration of SPC used. The optimized ethosomes were prepared from a dispersion of 4% w/v SPC:cholesterol:deoxycholic acid (6:2:1 M ratio) in 20% v/v ethanol in pH 7.4 phosphate buffer. The vesicular size was 55 ± 8 nm; the EE was 52.51% ± 4.09%, and the zeta potential was −39.06 ± 1.53 mV. These ethosomes led to significantly higher permeation of indomethacin through pig skin over 24 h than the commercial solution and the ethanolic solution of indomethacin. It was stable in terms of physical appearance, drug content, and EE when stored at ambient temperature for 3 months. These results indicated the feasibility of ethosomes as a transdermal drug carrier for indomethacin.

Membrane phospholipids remodeling upon imbibition in Brassica napus L. seeds

Successful seed germination depends on the rapid repair of cell membrane damaged by dry storage. However, little is known about the reorganization of lipids during this process. In this study, the changes of intracellular redox environment, cell membrane integrity, lipid composition, and expression of genes related to phospholipid metabolism were assessed during imbibition of Brassica napus seeds. A total number of 443 lipids belonging to 7 categories were detected by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). In the 24 h-imbibed seeds, the relative content of triacylglycerol was lower than in dry seeds, while the relative content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS), especially PC (36:2, number of carbons in the acyl chains: number of double bonds), PC (36:3), and PE (36:3) were higher than those in dry seeds. Meanwhile, the content and unsaturation levels of phospholipids increased, indicating membrane lipids remodeling during seed imbibition. The plasma membrane integrity, which was measured by the relative electrolyte leakage (REL) of the membrane and FM4-64 fluorescent dye, was improved upon imbibition, confirming that cell membrane was repaired after 24 h-imbibition. The reduction of H2O2 content, redox potential, and malondialdehyde (MDA) content indicated that the degree of membrane lipid peroxidation was significantly decreased upon imbibition. Gene expression analysis showed that the differential expression of genes for key enzymes occurred in the plateau phase of the imbibition curve, i.e. after 8 h-to 24 h-imbibition. Moreover, the differential expression of genes such as those encoding phospholipase C (PLC), phospholipase D (PLD), triacylglycerol lipase (TAG lipase), choline/ethanolamine phosphotransferase (CEPT), and phosphatidylserine synthase (PTDSS2) during imbibition indicated that membrane lipid remodeling was related to complex metabolic pathways, among which the degradation of triacylglycerol and the synthesis of phospholipids using diacylglycerol might play an important role during membrane remodeling.

Generation of transgenic zebrafish with 2 populations of RFP- and GFP-labeled thrombocytes: analysis of their lipids

AbstractZebrafish thrombocytes are similar to mammalian platelets. Mammals have young platelets (also called reticulated platelets) and mature platelets. Likewise, zebrafish have 2 populations of thrombocytes; one is DiI-C18 (DiI)+ (DP), and the other is DiI− (DN). However, the mechanism of selective thrombocyte labeling by DiI is unknown. Furthermore, there is no transgenic zebrafish line where DP and DN thrombocytes are differentially labeled with fluorescent proteins. In this study, we found that Glo fish, in which the myosin light chain 2 promoter drives the rfp gene, have a population of thrombocytes that are red fluorescent protein (RFP) labeled. We also generated transgenic GloFli fish in which DP and DN thrombocytes are labeled with RFP and green fluorescent protein (GFP), respectively. Single-cell lipid analysis showed a twofold increase in phosphatidylethanolamine (PE) and a twofold decrease in phosphatidylcholine (PC) in RFP+ thrombocytes compared with GFP+ thrombocytes, suggesting that lipid composition may be important for DiI differential labeling. Therefore, we tested liposomes prepared with different ratios of PC and PE and observed that liposomes prepared with higher amounts of PE favor DiI labeling, whereas the PC concentration had a modest effect. In liposomes prepared using only PE or PC, increased concentrations of PE resulted in increased DiI binding. These results suggest that because RFP+ thrombocytes have higher PE concentrations, DiI may bind to them efficiently, thus explaining the selective labeling of thrombocytes by DiI. This work also provides GloFli fish that should be useful in understanding the mechanism of thrombocyte maturation.

Correction of Cold Damage to Mammalian Erythrocytes by Chlorpromazine to Influence the Dynamic Structure of a Membrane

Abstract—The resistance of mammalian erythrocytes (human, dog, horse, bull, and rabbit) to cold shock in the presence of chlorpromazine was studied; its effect on the state of erythrocyte membranes was investigated. The bond strength between membrane phospholipids of mammalian erythrocytes and the characteristics of the cold shock of these cells was determined with the correlation analysis. It has been established that erythrocytes of mammals whose membranes contain a high content of sphingomyelin and phosphatidylethanolamine and a low content of phosphatidylcholines are more resistant to cold shock. Chlorpromazine showed high efficiency in protecting mammalian erythrocytes against cold shock. The dynamic structure of membranes of human erythrocytes treated with the chlorpromazine was studied by EPR of spin-probes. The use of a set of spin-labeled probes: palmitic acid amide, 5-DOXYL stearic acid, and 16-DOXYL stearic acid, which allow studying the micro-viscosity parameters of the lipid bilayer of erythrocyte membranes in the transmembrane direction, made it possible to establish the locations of chlorpromazine action, namely, in the region of polar heads and hydrophobic tails of membrane phospholipids.

Effect of Saline Soils on the Functional State of Species of the Genus Artemisia

The effect of saline soils on the functional state of glycohalophytes of the genus Artemisia (A. santonica, A. pauciflora, and A. lerchiana) in the basin of Lake Elton (Prieltonye) is studied. It is established that the higher levels of water and Na+ content in A. santonica leaves are correlated with a high content of pigments, carbohydrates, and phenolic compounds against the background of more intensive oxidative processes. It is noted that the accumulation of a significant amount of free amino acids is characteristic of the species A. pauciflora and A. lerchiana. At the level of structural components of membranes in A. pauciflora and A. lerchiana leaves, a high level of digalactosyldiacylglycerol and linolenic acid was recorded in the composition of the lipids of thylakoid membranes and an elevated concentration of phosphatidylcholine was found in nonplastid membranes.

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case-control sets from EPIC.

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow‐up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.

Choline Supplementation in Cystic Fibrosis-The Metabolic and Clinical Impact.

Background: Choline is essential for the synthesis of liver phosphatidylcholine (PC), parenchymal maintenance, bile formation, and lipoprotein assembly to secrete triglycerides. In choline deficiency, the liver accretes choline/PC at the expense of lung tissue, thereby impairing pulmonary PC homoeostasis. In cystic fibrosis (CF), exocrine pancreas insufficiency results in impaired cleavage of bile PC and subsequent fecal choline loss. In these patients, the plasma choline concentration is low and correlates with lung function. We therefore investigated the effect of choline supplementation on plasma choline/PC concentration and metabolism, lung function, and liver fat. Methods: 10 adult male CF patients were recruited (11/2014–1/2016), and orally supplemented with 3 × 1 g choline chloride for 84 (84–91) days. Pre-/post-supplementation, patients were spiked with 3.6 mg/kg [methyl-D9]choline chloride to assess choline/PC metabolism. Mass spectrometry, spirometry, and hepatic nuclear resonance spectrometry served for analysis. Results: Supplementation increased plasma choline from 4.8 (4.1–6.2) µmol/L to 10.5 (8.5–15.5) µmol/L at d84 (p < 0.01). Whereas plasma PC concentration remained unchanged, D9-labeled PC was decreased (12.2 [10.5–18.3] µmol/L vs. 17.7 [15.5–22.4] µmol/L, p < 0.01), indicating D9-tracer dilution due to higher choline pools. Supplementation increased Forced Expiratory Volume in 1 second percent of predicted (ppFEV1) from 70.0 (50.9–74.8)% to 78.3 (60.1–83.9)% (p < 0.05), and decreased liver fat from 1.58 (0.37–8.82)% to 0.84 (0.56–1.17)% (p < 0.01). Plasma choline returned to baseline concentration within 60 h. Conclusions: Choline supplementation normalized plasma choline concentration and increased choline-containing PC precursor pools in adult CF patients. Improved lung function and decreased liver fat suggest that in CF correcting choline deficiency is clinically important. Choline supplementation of CF patients should be further investigated in randomized, placebo-controlled trials.

Phospholipid profiles and hepatocellular carcinoma risk and prognosis in cirrhotic patients.

BackgroundHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Phospholipids are now well-recognised players in tumour progression. Their metabolic tissue alterations can be associated with plasmatic modifications. The aim of this study was to evaluate the potential of the plasma phospholipid profile as a risk and prognostic biomarker in HCC.MethodsNinety cirrhotic patients with (cases) or without HCC (controls) were studied after matching for inclusion centre, age, gender, virus infection, cirrhosis duration and Child-Pugh grade. High-performance liquid chromatography coupled with tandem-mass spectrometry was used to quantify the main species of seven categories of phospholipids in plasma.ResultsElevated concentrations of phosphatidylcholine (PC) 16:0/16:1 (p=0.0180), PC 16:0/16:0 (p=0.0327), PC 16:0/18:1 (p=0.0264) and sphingomyelin (SM) 18:2/24:1 (p=0.0379) and low concentrations of lysophosphatidylcholine 20:4 (0.0093) and plasmalogen-phosphatidylethanolamine (pPE) 16:0/20:4 (p=0.0463), pPE 18:0/20:4 (p=0.0077), pPE 18:0/20:5 (p=0.0163), pPE 18:0/20:3 (p=0.0463) discriminated HCC patients from cirrhotic controls. Two ceramide species were associated with increased HCC risk of death while lysophospholipids, a polyunsaturated phosphatidylinositol, some PC and SM species were associated with low risk of death in HCC patients in 1 and/or 3 years.ConclusionThis study identified phospholipid profiles related to HCC risk in liver cirrhotic patients and showed for the first time the potential of some phospholipids in predicting HCC patient mortality.