Phospholipids Phosphatidylcholine Research Articles

Phosphatidylethanolamine Synthesis Is Required for Optimal Virulence of Brucella abortus

The Brucella cell envelope contains the zwitterionic phospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Synthesis of PC occurs exclusively via the PC synthase pathway, implying that the pathogen depends on the choline synthesized by the host cell to form PC. Notably, PC is necessary to sustain a chronic infection process, which suggests that the membrane lipid content is relevant for Brucella virulence. In this study we investigated the first step of PE biosynthesis in B. abortus, which is catalyzed by phosphatidylserine synthase (PssA). Disruption of pssA abrogated the synthesis of PE without affecting the growth in rich complex medium. In minimal medium, however, the mutant required choline supplementation for growth, suggesting that at least PE or PC is necessary for Brucella viability. The absence of PE altered cell surface properties, but most importantly, it impaired several virulence traits of B. abortus, such as intracellular survival in both macrophages and HeLa cells, the maturation of the replicative Brucella-containing vacuole, and mouse colonization. These results suggest that membrane phospholipid composition is critical for the interaction of B. abortus with the host cell.

Interconnection of parameters of regulation system of lipid peroxidation and of morphophysiological parameters of mouse liver

A complex analysis of seasonal fluctuations of the mean group parameters of the system of regulation of lipid peroxidation has been performed in liver of Balb/c mice. Association of lipid characteristics and morphophysiological parameters is studied in the Balb/c mouse liver. An interconnection is revealed between the liver index and the amount of lysoforms of phospholipids, the scale and character of the interconnection differing essentially depending on proportion of phosphatidylcholine in mouse liver phospholipids.

The Pleckstrin Homology Domain of the Arf6-specific Exchange Factor EFA6 Localizes to the Plasma Membrane by Interacting with Phosphatidylinositol 4,5-Bisphosphate and F-actin

The Arf6-specific exchange factor EFA6 coordinates membrane trafficking with actin cytoskeleton remodeling. It localizes to the plasma membrane where it catalyzes Arf6 activation and induces the formation of actin-based membrane ruffles. We have shown previously that the pleckstrin homology (PH) domain of EFA6 was responsible for its membrane localization. In this study we looked for the partners of the PH domain at the plasma membrane. Mutations of the conserved basic residues suspected to be involved in the binding to phosphoinositides redistribute EFA6-PH to the cytosol. In addition, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) breakdown also leads to the solubilization of EFA6-PH. Direct binding measured by surface plasmon resonance gives an apparent affinity of approximately 0.5 microm EFA6-PH for PI(4,5)P2. Moreover, we observed in vitro that the catalytic activity of EFA6 is strongly increased by PI(4,5)P2. These results indicate that the plasma membrane localization of EFA6-PH is based on its interaction with PI(4,5)P2, and this interaction is necessary for an optimal catalytic activity of EFA6. Furthermore, we demonstrated by fluorescence recovery after photobleaching and Triton X-100 detergent solubility experiments that in addition to the phophoinositides, EFA6-PH is linked to the actin cytoskeleton. We observed both in vivo and in vitro that EFA6-PH interacts directly with F-actin. Finally, we demonstrated that EFA6 could bind simultaneously filamentous actin and phospholipids vesicles. Our results explain how the exchange factor EFA6 via its PH domain could coordinate at the plasma membrane actin cytoskeleton organization with membrane trafficking.

Histones interact with anionic phospholipids with high avidity; its relevance for the binding of histone-antihistone immune complexes.

Antibodies recognizing anionic phospholipids have been described in systemic lupus erythematosus (SLE) and other autoimmune diseases. Recent studies have shown that some of these antibodies may recognize a cardiolipin-binding protein (apolipoprotein H) rather than phospholipids. A similar possibility is conceivable for other cardiolipin-binding proteins that are targets of autoantibodies. In this study we have addressed whether this might be the case for histones, a set of highly cationic and widely distributed proteins that react in a well known autoantibody system. Our results indicate that: (i) histones bind to anionic phospholipids (cardiolipin and phosphatidylserine) with high avidity, but not to zwitterionic phospholipids (phosphatidylcholine); (ii) monoclonal and polyclonal antihistone antibodies recognize histones bound to cardiolipin; (iii) the addition of histones to serum samples containing antihistone antibodies often enhances their anticardiolipin reactivity. In addition, we have found that antihistone-producing hybridomas derived from MRL-lpr mice may show anticardiolipin activity due to the presence of histones in the cell culture supernatants with the resultant formation of immune complexes. Taken together, the results suggest a potential role for histones in the anti-cardiolipin activity detected in sera containing antihistone antibodies. These histone-phospholipid interactions should be taken into account when evaluating the pathogenic effects of antihistone antibodies or other autoantibodies reacting with nuclear components (e.g. nucleosomes) containing histones.

Environmentally Friendly Slow Release Formulations of Alachlor Based on Clay-Phosphatidylcholine

A new clay-liposome complex was developed for reducing leaching of herbicides and contamination of groundwater. The liposomes were composed of the neutral and Environmental Protection Agency approved phospholipid phosphatidylcholine (PC). Adsorption of PC liposomes on the clay mineral montmorillonite could exceed the cation exchange capacity of the clay, and was well simulated by the Langmuir equation. X-ray diffraction results for 6 mM PC and 1.6 g/L clay (3 day incubation) yielded a basal spacing of 7.49 nm, which was interpreted as the formation of a supported planar bilayer on montmorillonite platelets. Fluorescence methods demonstrated structural changes which reflected adsorption of PC followed by loss of vesicle integrity as measured by the penetration of dithionite into the internal monolayer of fluorescently labeled liposomes, resulting in a decrease in fluorescence intensity to 18% of initial after 4 h. Energy transfer was demonstrated after 1 h from labeled liposomes to montmorillonite labeled by an acceptor. The neutral herbicide alachlor adsorbed on the liposome-clay complex, yielding a formulation of up to 40% active ingredient, and 1.6-fold reduction in herbicide release in comparison to the commercial formulation. Hence, the PC-montmorillonite complex can form a basis for environmentally friendly formulations of herbicides, which would yield reduced leaching.

Phosphorylation of the yeast lipin homolog Pah1p by Cdc28p kinase

The yeast lipin homolog Pah1p is a Mg2+‐dependent phosphatidate phosphatase enzyme that catalyzes the dephosphorylation of phosphatidate to diacylglycerol and Pi. Pah1p is responsible for de novo lipid synthesis, its reaction being the committed step for the synthesis of the storage lipid triacylglycerol, which is formed from phosphatidate via diacylglycerol. The diacylglycerol generated in the phosphatidate phosphatase reaction is also utilized in the synthesis of the membrane phospholipids phosphatidylcholine and phosphatidylethanolamine via the Kennedy Pathway. Previous studies indicate that Pah1p is phosphorylated by cyclin‐dependent Cdc28p kinase and dephosphorylated by the Nem1p‐Spo7p phosphatase complex. A phosphorylation‐deficient Pah1p mutant exhibits elevated phosphatidate phosphatase activity suggesting that phosphorylation inhibits activity. In this work, we examined the phosphorylation of Pah1p by Cdc28p kinase in vitro. Using purified Escherichia coli‐expressed Pah1p as a substrate, Cdc28p kinase activity was dependent on the time of phosphorylation and the concentration of the kinase. In addition, Cdc28p kinase activity was dependent on the concentration of Pah1p and ATP. Serine and threonine residues were targets for phosphorylation. The phosphorylation of Pah1p resulted in the loss of its phosphatidate phosphatase activity. Supported by NIH grant GM‐28140.

Phosphatidylcholine synthesis is required for optimal function of Legionella pneumophila virulence determinants

The function of phosphatidylcholine (PC) in the bacterial cell envelope remains cryptic. We show here that productive interaction of the respiratory pathogen Legionella pneumophila with host cells requires bacterial PC. Synthesis of the lipid in L. pneumophila was shown to occur via either phospholipid N-methyltransferase (PmtA) or phosphatidylcholine synthase (PcsA), but the latter pathway was demonstrated to be of predominant importance. Loss of PC from the cell envelope caused lowered yields of L. pneumophila within macrophages as well as loss of high multiplicity cytotoxicity, while mutants defective in PC synthesis could be complemented either by reintroduction of PcsA or by overproduction of PmtA. The lowered yields and reduced cytotoxicity in mutants with defective PC biosynthesis were due to three related defects. First, there was a poorly functioning Dot/Icm apparatus, which delivers substrates required for intracellular growth into the cytosol of infected cells. Second, there was reduced bacterial binding to macrophages, possibly due to loss of PC or a PC derivative on the bacterium that is recognized by the host cell. Finally, strains lacking PC had low steady-state levels of flagellin protein, a deficit that had been previously associated with the phenotypes of lowered cytotoxicity and poor cellular adhesion.

Cholesterol and anionic phospholipids increase the binding of amyloidogenic transthyretin to lipid membranes

Deposition of transthyretin (TTR) amyloid is a pathological hallmark of familial amyloidotic polyneuropathy (FAP). Recently we showed that TTR binds to membrane lipids via electrostatic interactions and that membrane binding is correlated with the cytotoxicity induced by amyloidogenic TTR. In the present study, we examined the role of lipid composition in membrane binding of TTR by a surface plasmon resonance (SPR) approach. TTR bound to lipid bilayers through both high- and low-affinity interactions. Increasing the mole fraction of cholesterol in the bilayer led to an increase in the amount of high-affinity binding of an amyloidogenic mutant (L55P) TTR. In addition, a greater amount of L55P TTR bound with high affinity to membranes made from anionic phospholipids, phosphatidylglycerol (PG) and phosphatidylserine (PS), than to membranes made from zwitterionic phospholipid phosphatidylcholine (PC). The anionic phospholipids (PS and PG) promoted the aggregation of L55P TTR by accelerating the nucleation phase of aggregation, whereas the zwitterionic phospholipid PC had little effect. These results suggest that cholesterol and anionic phospholipids may be important for TTR aggregation and TTR-induced cytotoxicity.

Lipids of human meibum: mass-spectrometric analysis and structural elucidation

The purpose of this study was to structurally characterize the major lipid species present in human meibomian gland secretions (MGS) of individual subjects by means of ion trap atmospheric pressure ionization mass spectrometry analysis (API MS(n)). The samples of MGS and authentic lipid standards were analyzed in direct infusion and high-pressure liquid chromatography (HPLC) experiments with API MS(n) detection of the analytes (HPLC API MS(n)). The major precursor ions were isolated and subjected to further sequential fragmentation in MS(n) experiments, and their fragmentation patterns were compared with those of authentic lipid standards. Multiple precursor ions were observed in the positive-ion mode. Among those, previously identified cholesterol (Chl; m/z 369; [M - H(2)O + H](+)) and oleic acid (OA; m/z 283; [M + H](+)) were found. The other major compounds of the general molecular formula C(n)H(2n-2)O(2) were consistent with wax esters (WEs), with OA as fatty acyl component. Accompanying them were two homologous series of compounds that fit the molecular formulas C(n)H(2n-4)O(2) and C(n)H(2n)O(2). Subset 2 was found to be a homolog series of linoleic acid-based WEs, whereas subset 3 was, apparently, a mixture of stearic acid-based WEs. HPLC API MS(n) analysis revealed the presence of large quantities of cholesteryl esters (Chl-Es) in all of the tested samples. Less than 0.1% (w/w) of oleamide was detected in human MGS. In the negative-ion mode, three major compounds with m/z values of 729, 757, and 785 that were apparently related to anionogenic lipids of the diacylglyceryl family were found in all of the samples. Common phospholipids and ceramides (Cers) were not present among the major MGS lipids. Phosphocholine-based lipids were found in MGS in quantities less than 0.01% (w/w), if at all. This ratio is two orders of magnitude lower than reported previously. These observations suggest that MGS are a major source of nonpolar lipids of the WE and Chl-E families for the tear film lipid layer, but not of its previously reported (phospho)lipid, Cer, and fatty acid amide components.

Changes in the lipid class and proximate compositions of coho salmon ( Oncorhynchus kisutch) smolts infected with the nematode parasite Philonema agubernaculum

Coho salmon ( Oncorhynchus kisutch) smolts infected with the nematode Philonema agubernaculum had 36% lower mean lipid content (1.4%) than nonparasitized coho salmon (2.2%) harvested simultaneously from the same outmigration. Lengths, weights, and condition factors, as well as protein and moisture content, did not differ significantly between the two groups. Lipid class compositions differed significantly between the parasitized and nonparasitized fish. None of the nematode-infected fish contained detectable triacylglycerols (TAG) or monoacylglycerols (MAG). In contrast, mean TAG and MAG contents of the nonparasitized fish totaled 5.5% of the extracted lipid. Infected smolts had lower cholesterol contents than did uninfected coho (17% for infected, 33% for uninfected). Parasitized fish had significantly higher levels of free fatty acids (mean of 57% for parasitized vs. 35% for nonparasitized) as well as the phospholipids phosphatidylethanolamine (PE) and phosphatidylcholine (PC). However, the PC/PE ratios for infected and noninfected coho did not differ significantly (2.2 for infected vs. 2.0 for uninfected). These differences suggest that the parasitic nematodes are either harvesting storage energy directly from the coho or are placing additional energetic demands on the fish to cope with the infection.

Oxidative lipidomics of γ-irradiation-induced intestinal injury

Although γ-irradiation-induced tissue injury has been associated with lipid peroxidation, the individual phospholipid molecular targets have not been identified. We employed oxidative lipidomics to qualitatively and quantitatively characterize phospholipid peroxidation in a radiosensitive tissue, the small intestine, of mice exposed to total body irradiation (TBI) (10 and 15 Gy). Using electrospray ionization mass spectrometry we found that the major classes of intestine phospholipids—phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol—included clusters with highly oxidizable molecular species containing docosahexaenoic fatty acid. Molecular species of cardiolipin were represented by only two major less oxidizable individual molecular species—tetralinoleoylcardiolipin and trilinoleoyl-mono-oleoylcardiolipin. Selective and robust oxidation of two anionic phospholipids—cardiolipin in mitochondria and phosphatidylserine outside of mitochondria—was observed 24 h after γ-irradiation. MS analysis detected several TBI-induced molecular species of oxidized cardiolipin: (C 18:2) 3(C 18:2–OOH), (C 18:2) 2(C 18:2–OOH) 2, (C 18:2) 1(C 18:2–OOH) 3, and (C 18:2–OOH) 4. The major molecular species involved in TBI-triggered peroxidation of phosphatidylserine included C 18:0/C 22:6–OOH, C 18:0/C 22:5–OOH, and C 18:0/C 22:4–OOH. More abundant phospholipids—phosphatidylcholine and phosphatidylethanolamine—did not reveal any oxidative stress responses despite the presence of highly oxidizable docosahexaenoic fatty acid residues in their molecular species. A marked activation of caspases 3/7 that was detected in the intestine of γ-irradiated mice indicates the involvement of apoptotic cell death in the TBI injury. Given that oxidized molecular species of cardiolipin and phosphatidylserine accumulate during apoptosis of different cells in vitro we speculate that cardiolipin and phosphatidylserine oxidation products may be useful as potential biomarkers of γ-irradiation-induced intestinal apoptosis in vivo and may represent a promising target for the discovery of new radioprotectors and radiosensitizers.

Reduction of gangliosides, phospholipids and cholesterol content in cerebral cortex of rats caused by chronic hypermethioninemia

Neurological dysfunction is observed in patients with severe hypermethioninemia, whose physiopathology is still poorly understood. In the current study we investigated the effect of chronic administration of methionine on the content and species of gangliosides and phospholipids, as well as on the concentration of cholesterol in rat cerebral cortex. Wistar rats received subcutaneous injections of methionine (1.34–2.68μmol/g of body weight), twice a day, from the 6th to the 28th day of age and controls received saline. Animals were killed 12h after the last injection. Results showed that methionine administration significantly decreased the total content of lipids in cerebral cortex of rats. We also observed that this amino acid significantly reduced the absolute quantity of the major brain gangliosides (GM1, GD1a, GD1b and GT1b) and phospholipids (sphingomyelin, phosphatidylcholine and phosphatidylethanolamine). We also showed that Na+,K+-ATPase activity and TBARS were changed in cerebral cortex of rats subjected to hypermethioninemia. If confirmed in human beings, these data could suggest that the alteration in lipid composition, Na+,K+-ATPase activity and TBARS caused by methionine might contribute to the neurophysiopathology observed in hypermethioninemic patients.

Alterations of the composition and metabolism of pulmonary surfactant phospholipids induced by experimental peritonitis in rats

Pulmonary complications often accompany the development of acute peritonitis. In this study, we analyzed the alterations of alveolar surfactant phospholipids in rats with experimentally induced peritonitis. The results showed a reduction of almost all phospholipid fractions in pulmonary surfactant of experimental animals. The most abundant alveolar phospholipids—phosphatidylcholine and phosphatidylglycerol were reduced significantly in surfactant of rats with experimental peritonitis. In addition, analysis of the fatty acid composition of these two phospholipids revealed marked differences between experimental and control animals. The activity of phospholipase A2, which is localized in the hydrophyllic phase of alveolar surfactant, was higher in rats with experimental peritonitis compared to sham-operated ones. Also, a weak acyl-CoA:lysophospholipid acyltransferase activity was detected in alveolar surfactant of rats with experimental peritonitis, whereas in control animals this activity was not detectable. The lipid-transfer activity was quite similar in pulmonary surfactant of control and experimental rats. The total number of cells and the percentage of neutrophils were strongly increased in broncho-alveolar lavage fluid from rats with peritonitis. Thus, our results showed that the development of peritonitis was accompanied by pulmonary pathophysiological processes that involved alterations of the phospholipid and fatty acid composition of alveolar surfactant. We suggest that the increased populations of inflammatory cells, which basically participate in internalization and secretion of surfactant components, contributed to the observed alterations of alveolar phospholipids. These studies would be useful for clarification of the pathogenic mechanisms underlying the occurrence of pulmonary disorders that accompany acute inflammatory conditions, such as peritonitis and sepsis.

Phospholipid mediated plasticity in exocytosis observed in PC12 cells

Membrane composition serves to identify intracellular compartments, signal cell death, as well as to alter a cell's electrical and physical properties. Here we use amperometry to show that supplementation with the phospholipids phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), and phosphatidylserine (PS) can alter several aspects of exocytosis. Changes in the amperometric peak shape derived from individual exocytosing vesicles reveal that PC slows expulsion of neurotransmitter while PE accelerates expulsion of neurotransmitter. Amperometry data reveal a reduced amount of catecholamine released per event from PC-treated cells while electron micrographs indicate the vesicles in these cells are 50% larger than controls, thus providing evidence of pharmacological changes in vesicle concentration. Addition of SM appears to affect the rate of fusion pore expansion, indicated by slower peak rise times, but does not affect decay times or quantal size. Addition of PS results in a 1.7-fold increase in the number of events elicited by high-K + depolarization. Electron micrographs of PS-treated cells suggest that increased vesicle recruitment underlies enhanced secretion. We did not observe any effect of phosphatidylinositol (PI) treatment. Together these data suggest that differences in membrane composition affect exocytosis and might be involved in mechanisms of cell function controlling the dynamics of communication via exocytosis.

Caprine cardiac sarcoplasmic reticulum isolation and biochemical characterisation with emphasis on Ca(2+)-adenosine triphosphatase.

This study was aimed at isolating, in its pure form, and characterizing the sarcoplasmic reticulum from caprine (Capra hircus) heart. The sarcoplasmic reticulum from thirty caprine heart ventricular homogenates was isolated and purified. It was characterized on the basis of both, its protein and lipid composition. The protein content was 142±10 mg/g of tissue. Ca(2+)-ATPase activity equaled 3.75±1.06mmol Pi/mg protein/min while the uptake rate was 24±1.14 nmol/mg protein/min. 205kD, 110kD, 90kD, 84kD, 66kD, 55kD and 29kD molecular weight proteins were seen on an SDS polyacrylamide gel. Triglyceride, Cholesterol and Phospholipids (phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine, sphingomyelin and phosphatidylserine) were present in increasing order of their concentration. Long chain fatty acids predominated over the unsaturated ones. The ryanodine receptor displayed two binding sites for ryanodine. Characterisation encompassing the above biochemical aspects of normal caprine cardiac sarcoplasmic reticulum was thus achieved after isolating it in the pure form.

Relationships between sterol/phospholipid composition and xenobiotic transport in nematodes

Therapeutic failure limits prophylaxis of nematode diseases and has been mainly attributed to mutations in cellular targets of anthelmintics. Besides these specific mechanisms, alterations of drug transport also occur in parasites resistant to anthelmintics and depend on both the presence of membrane pumps such as P-glycoprotein (Pgp) and on the lipid composition of membranes. We recently showed in the nematode Haemonchus contortus, using eggs as a model, that the total cholesterol (TC) concentration alters the transport of lipophilic molecules due to membrane pumps such as P-glycoprotein and the resistance to anthelmintics. The effect of TC may depend on the presence of other lipids interacting with TC. Therefore, we analysed the lipid composition and its relationship with Pgp and resistance to anthelmintics. Better correlations were found between Pgp and free cholesterol (FC) than with TC. We also showed that the relationships between lipid composition and resistance to anthelmintics or Pgp depended on the equilibrium between FC and phospholipids (PLs), mainly PLs known to be present primarily in either the external leaflets of cell membranes or the internal leaflets. The PLs phosphatidylcholine and phosphatidylethanolamine played the most significant role, but phosphatidic acid also influenced drug resistance.

Targeting Nutrient Uptake Mechanisms in Plasmodium

The proliferation of the intraerythrocytic malaria parasite is dependent on the uptake from the blood plasma, and from the cytoplasm of the host cell, of a range of essential nutrients. These compounds are taken up into the parasitised cell via a combination of constitutively active endogenous host cell transporters and new parasite-induced permeability pathways. On entering the infected cell they are taken up by the intracellular parasite, across the parasitophorous vacuole and parasite plasma membranes, via a combination of channels and transporters, and/or via endocytosis. Once inside the parasite, nutrients are typically phosphorylated and thereby effectively trapped within the cell. The intraerythrocytic parasite has a range of subcellular membrane-bound organelles, each endowed with their own complement of transport proteins which mediate the uptake and efflux of metabolic substrates and byproducts. Proteins that mediate the uptake, intracellular trafficking and metabolism of essential nutrients in the Plasmodium-infected erythrocyte are potential antimalarial drug targets. Here we consider the nature of the pathways involved, focusing in particular on those that mediate the uptake of three important nutrients: glucose, the key energy-substrate for the parasite; pantothenate (vitamin B(5)), the precursor of the important enzyme cofactor, coenzyme A; and choline, the precursor of the phospholipid phosphatidylcholine.

Developmental establishment of epigenotype: a role for dietary fatty acids?

Human epidemiologic data indicate that nutrition during prenatal and early postnatal development can affect susceptibility to various chronic diseases in adulthood (the developmental origins hypothesis). Controlled studies in animal models corroborate that nutritional exposures during critical periods of development wield lasting influences on gene expression and metabolism, but our understanding of the fundamental biological mechanisms underlying such phenomena remains rudimentary. Nutritional influences on the developmental establishment of epigenetic gene regulatory mechanisms could link early nutrition to adult chronic disease susceptibility. Just as genetic variation contributes to individual susceptibility to chronic disease, it is increasingly evident that so too does epigenetic variation. Very little is known about the factors that contribute to interindividual variation in epigenotype. It is critically important to determine whether nutrition and other en vironmental influences during development affect the establishment of human epigenotype. Most previous studies of nutritional influences on epigenetic regulation have focused on nutrients known to affect one-carbon metabolism. For example, supplementation during development with methyl donors including folic acid and vitamin B12 appears to induce DNA hypermethylation at specific loci by increasing the flux through the DNA methylation pathway. This article will consider the mechanisms by which fatty acid nutrition during prenatal and early postnatal nutrition might affect the establishment of epigenetic gene regulatory mechanisms. Choline, a component of the phospholipid phosphatidylcholine, stands at the intersection of lipid and one-carbon metabolism; upon conversion to betaine, its three methyl groups are available to one-carbon metabolism. Potentially much more important than providing methyl groups for DNA methylation, dietary fatty acids could affect the establishment o f epigenetic mechanisms by stimulating transcription of specific genes during critical developmental windows. For example, the peroxisome proliferator activated receptor-a (PPAR-a) transcription factor is activated by a variety of fatty acids to transactivate specific genes. PPAR-amediated transcriptional activation during critical ontogenic periods could impede epigenetic silencing of genes involved in fatty acid metabolism. Lastly, recent data indicate that lipids and lipoprotein components interact directly with chromatin structure to influence gene expression. Hence, intake of specific dietary fatty acids during development could induce persistent changes in gene expression by altering the establishment of epigenetic mechanisms. Keywords: DNA methylation, Developmental origins, Epigenetics, Metabolic imprinting, Nutrition

Effects of Factor Xa and Protein S on the Individual Activated Protein C-mediated Cleavages of Coagulation Factor Va

Effects of Factor Xa and Protein S on the Individual Activated Protein C-mediated Cleavages of Coagulation Factor Va

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of cardiolipin extracted from detergent-solubilized mitochondrial electron transfer complexes

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of cardiolipin extracted from detergent-solubilized mitochondrial electron transfer complexes