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PubMed2003

EPR studies of phospholipid bilayers after lipoperoxidation. 1. Inner molecular order and fluidity gradient.

The molecular order of fatty acyl chains in oriented lipid bilayers on solid support (SPB), made of either natural or synthetic phospholipids oxidized by Fenton reagent and probed with spin labeled lecithin (5-DSPC) was studied by means of EPR spectrometry. Phospholipids (ASPC, EYPC, mitochondrial extract) were oxidized as either aqueous buffer/methanol dispersions or reverse-phase evaporation vesicles (REV) suspensions. Oxidation was preliminarily revealed both by assaying MDA and by detecting conjugated dienes. Oxidized phospholipid species was quantified by preparative TLC. The degree of order in oriented lipid bilayers of samples containing oxidized phospholipids was estimated by the loss of EPR spectral anisotropy, and an empirical index of the related bilayer disorder was calculated from the second derivative spectra. Bilayers made of each non-oxidized phospholipid species from either ethanol solutions or REV suspensions showed the highest anisotropy, while the increasing presence of oxidized lipids in the samples resulted in progressive loss of EPR spectral anisotropy. In contrast, vesicles containing 40% of the oxidized species maintained an unaltered fluidity gradient, while REV formation was hindered by oxidized phospholipid percentages higher than 45% for ASPC and EYPC, and 35% for Mitochondrial lipids (MtL). It is concluded that the early stages of lipoperoxidation bring about disordering of the phospholipid bilayer interior rather than fluidity alterations, and that prolonged oxidation may result in loss of structural and chemical properties of the bilayer until the structure no longer holds.

Animals↗
PubMed1997

Minimal oxidation and storage of low density lipoproteins result in an increased susceptibility to phospholipid hydrolysis by phospholipase A2.

In vitro-studies have shown that phospholipid hydrolysis of low density lipoproteins (LDL) by bee venom or porcine pancreatic phospholipase A2 (PLA2) leads to an increased uptake of these lipoproteins by macrophages transforming them into foam cells. Recently, a secretory phospholipase A2, group II, was detected in human atherosclerotic plaques. In order to investigate the role of this enzyme in the pathogenesis of atherosclerosis, a structurally identical human secretory PLA2 was purified from the medium of HepG2 cells stimulated with interleukin-6 and tumor necrosis factor-alpha. The activity of the purified enzyme towards the phospholipids of native and modified low density lipoproteins was compared with the activity towards Escherichia coli-membranes and other phospholipid substrates. Compared to E. coli-membranes, native LDL proved to be a poor substrate for group II PLA2. After mild oxidation induced by copper ions or by 2,2-azobis(2-amidinopropane) (AAPH), the susceptibility of LDL to phospholipid hydrolysis was found to be increased by 25 and 23%, respectively, whereas extensive copper-mediated oxidation caused a decreased hydrolysis. Aging of LDL at 6 degrees C for weeks or at 37 degrees C for hours resulted in an increase in PLA2-catalyzed phospholipid hydrolysis of up to 26-fold. LDL protected from oxidation by probucol during aging showed a lesser increase in susceptibility to phospholipid hydrolysis. Our results suggest that PLA2, group II, can increase the atherogenicity of LDL by its ability to hydrolyze the phospholipids of these lipoproteins, especially after modifications that are likely to occur in vivo.

Cell Line↗
PubMed2003

Phospholipids in parasitic protozoa.

Parasitic protozoa are surrounded by membrane structures that have a different lipid and protein composition relative to membranes of the host. The parasite membranes are essential structurally and also for parasite specific processes, like host cell invasion, nutrient acquisition or protection against the host immune system. Furthermore, intracellular parasites can modulate membranes of their host, and trafficking of membrane components occurs between host membranes and those of the intracellular parasite. Phospholipids are major membrane components and, although many parasites scavenge these phospholipids from their host, most parasites also synthesise phospholipids de novo, or modify a large part of the scavenged phospholipids. It was recently shown that some parasites like Plasmodium have unique phospholipid metabolic pathways. This review will focus on new developments in research on phospholipid metabolism of parasitic protozoa in relation to parasite-specific membrane structures and function, as well as on several targets for interference with the parasite phospholipid metabolism with a view to developing new anti-parasitic drugs.

Animals↗
PubMed1997

Phospholipids and their fatty acids in infective juveniles of entomopathogenic steinernematid nematodes.

The composition of phospholipids and their fatty acids was investigated in the infective juveniles (IJs) of four species of entomopathogenic nematodes: Steinernema carpocapsae (strain All), S. riobravis (strain Biosys 355), S. feltiae (strain UK76) and S. glaseri (strain NC). In newly emerged IJs of the four species, phospholipids comprised 15-18% dry weight of the total lipids (or 5-6% dry weight of the nematode), and phosphatidylethanolamine and phosphatidylcholine constituted about 40 and 30%, respectively, of the total phospholipids, with phosphatidylserine (PS) and phosphatidylinositol (PI) collectively accounting for about 25%. Qualitatively, the four species had identical total phospholipid (combined non-acidic and acidic fractions) fatty acid profiles, although there were some differences in the relative proportions (mol%) of specific fatty acids. The fatty acid composition of the total phospholipids in newly emerged IJs was dominated by C16 fatty acids, specifically C16:0 (14-18%), C16:1n-7 (up to 20%) and C16:4 (up to 26%), whereas the major C18 fatty acid was C18:1n-9 (20-23%). Polyunsaturated C20 fatty acids collectively made up 8-13% of the total composition. When newly emerged IJs were stored in distilled water at 25 degrees C, the proportions of C16:0 and C16:4 decreased with storage time, whereas C16:3n-3 increased (by 30-fold in S. glaseri). These changes were mostly observed in the acidic phospholipid fraction (mainly PI and PS). No evidence was found for a correlation between the fatty acid composition of the phospholipids and the relative ability of the IJs of the four Steinernema species to survive desiccation stress.

Animals↗
PubMed2000

Alternative pathways for phospholipid synthesis in different brain areas during aging.

Morphological and biochemical changes take place in the membrane of aged brain. In particular, studies on aged rats report alterations in brain phospholipid synthesis and in phospholipid-specific fatty acid composition. However, no significant changes in main phospholipid class content have been reported in aged brain, possibly owing to alterations in the alternative pathways for phospholipid synthesis during aging. Therefore, the present study was designed to determine the effect of aging on the enzyme activities responsible for phospholipid synthesis by alternative pathways. Indifferent brain areas of adult (3.5-month-old) and aged (28.5-month-old) rats we examined: 1) the activity of base exchange enzymes, which is a calcium-dependent, energy-independent and calcium stimulated enzymatic pathway; 2) phosphatidylethanolamine (PE) synthesis by phosphatidylserine decarboxylase activity (PSD); 3) phosphatidylcholine (PC) synthesis by transfer of methyl groups to endogenous PE by phosphatidylethanolamine N-methyltransferase activity (PEMT); 4) the synthesis of phosphatidylglycerol (PG) through phospholipase D (PLD) activity. Because the dependence on and the stimulation by calcium of base-exchange reactions is a well known mechanism and alterations in calcium levels in rat brain have been reported, we decided to investigate PS synthesis in the presence of endogenous and exogenous calcium (2.5mM). PS synthesis increased in cerebral cortex (CC) and cerebellum (CRBL) of aged rats with respect to adult rats in basal conditions (without the addition of exogenous calcium), but more significant changes were observed in serine base exchange activity during aging when exogenous calcium was added. PEMT activity in aged CC increased by 100%, the principal modification being observed in the first methylated product of the sequential reaction. Furthermore, the transphosphatidyl reaction was higher in aged brain as indicated by the increased PG synthesis. Our findings allow us to conclude that age affects some alternative pathways for phospholipid synthesis in the central nervous system, and indicate the presence of a compensatory mechanism to provide a pool of phospholipid classes for the maintenance of cellular membrane lipid composition during aging.

Aging↗
PubMed1998

Arginine vasopressin stimulates phospholipid methylation in cultured rat mesangial cells: possible role for PGE2 production.

Incorporation of [3H-methyl] groups into phospholipids and prostaglandin E2 (PGE2) production in cultured rat mesangial cells were examined in the presence and absence of arginine vasopressin (AVP). In cells stimulated with AVP, a rapid increase in the incorporation of [3H-methyl] group into phospholipids was observed within 1 min after stimulation. The [3H-methyl] group present in the phospholipids began to decline 2.5 min after stimulation. The production of PGE2 increased with AVP treatment, and the decline in methylated phospholipids paralleled the release of PGE2 in AVP-stimulated cells. The inhibition of phospholipid methylation by treatment with adenosyl-S-isobutyl mercaptan (SIBA) resulted in a marked decrease in AVP-stimulated PGE2 production. In order to determine the identity of the methylated phospholipids, [3H-methyl] incorporation into phosphatidylethanolamine derivatives was examined. In AVP-stimulated cells, an increase of [3H-methyl] labeled phosphatidylcholine and lysophosphatidylcholine was observed after stimulation with AVP, followed by an apparent increase of [3H-methyl] labeled lysophosphatidylcholine. These findings indicate that AVP stimulates phospholipid methylation in cultured rat mesangial cells and phosphatidylcholine, synthesized by a transmethylation pathway, may be a source for PGE2 production.

Animals↗
PubMed2000

Aldosterone alters the phospholipid composition of rat colonocytes.

Previous studies have shown that aldosterone treatment of amphibian epithelial cells results not only in stimulation of Na(+) absorption but also in changes in phospholipid composition which are necessary for the mineralocorticoid action of aldosterone. The present study was designed to investigate the effect of aldosterone on phospholipids of mammalian epithelia. Phospholipid and fatty acid composition was examined in colonic epithelium (mineralocorticoid target tissue) and thymus (non-mineralocorticoid but glucocorticoid target tissue) of rats which had received aldosterone or vehicle by a miniosmotic pump for 7 days. Aldosterone increased the mass of colonic phospholipids relative to cellular proteins with concomitant changes in the percentage distribution of fatty acids, whereas the relative distribution of membrane phospholipds was not changed. Phosphatidylcholine increased the content of polyunsaturated and decreased that of monounsaturated fatty acids, which predominantly reflected the accretion of arachidonic and a decrease in oleic and palmitoleic acids. Within the phosphatidylethanolamine subclass, pretreatment of rats with aldosterone decreased the content of monounsaturated fatty acids (predominantly oleic and palmitoleic acid) and of n-3 fatty acids, and increased the content of saturated fatty acids (palmitic acid). The saturated-to-nonsaturated fatty acid ratio also significantly increased after aldosterone treatment. No changes in thymic phospholipids were seen. The results are consistent with the contention that aldosterone specifically modulates phospholipid concentration and metabolism in mineralocorticoid target tissue. The changes in phospholipid content and its fatty acid composition during the fully developed effect of aldosterone may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function.

Aldosterone↗
PubMed1995

Efflux of cellular cholesterol and phospholipid to lipid-free apolipoproteins and class A amphipathic peptides.

The mechanism(s) by which lipid-free apolipoprotein (apo) AI is able to stimulate efflux of cholesterol and phospholipid from cells in cultures has (have) been examined. This process was found to be enhanced when macrophages were enriched with cholesterol. There were 12- and 4-fold increases in cholesterol and phospholipid efflux, respectively, from cholesterol-enriched mouse macrophages when compared to cells not loaded with cholesterol. This enhancement in cholesterol efflux to lipid-free apo AI from macrophages enriched with cholesterol was found to be controlled by the level of free cholesterol in the cells. When cholesterol-enriched mouse macrophages were exposed to lipid-free apo AI at 20 micrograms/mL (706 nM), there was significant efflux of [14C]cholesterol and [3H]phospholipid (20% +/- 0.5%/24 h and 6% +/- 0.3%/24 h, respectively). In comparison, HDL at equivalent protein concentrations only stimulated 11% and 4% efflux of cholesterol and phospholipid, respectively. Synthetic peptides containing amphipathic helical segments that mimic those present in apo AI were used to examine the structural features of the apoprotein which stimulate lipid efflux. Peptides containing only one (18A) or two (37pA) amphipathic helical segments stimulated as much cholesterol efflux from both mouse macrophages and L-cells as apo AI. The order of efficiency, as assessed by the mass concentration at which half-maximal efflux was reached (EC50), was apo AI > 37pA > 18A, indicating that acceptor efficiency was dependent on the number of amphipathic helical segments per molecule. When the helical content of 18A was increased by neutralizing the charges at the ends of the peptide (Ac-18A-NH2), there was a substantial increase in the efficiency for cholesterol efflux (EC50 18A = 17 micrograms/mL vs Ac-18A-NH2 = 6 micrograms/mL). In contrast, when the amphipathicity of the helix in 18A was decreased by scrambling the amino acid sequence, thereby reducing its lipid affinity, cholesterol and phospholipid efflux were not stimulated. The efficiency with which the peptides stimulated cholesterol efflux was in order of their lipid affinity (37pA > Ac-18A-NH2 > 18A), and this order was similar for phospholipid efflux. The time course of lipid release from mouse macrophages and L-cells indicated that phospholipid appeared in the extracellular medium before cholesterol. These results suggest that the apo AI or peptides first interacted with the cell to form protein/phospholipid complexes, that could then accept cholesterol.

Amino Acid Sequence↗
PubMed1993

Contribution of hydrogen bonding to lipid-lipid interactions in membranes and the role of lipid order: effects of cholesterol, increased phospholipid unsaturation, and ethanol.

It is proposed that increased phospholipid unsaturation in membranes and perturbation by agents such as ethanol weaken interlipid hydrogen bonding involving water and that the process is independent of effects on lipid order. To investigate this, the rates of phospholipid desorption, as a measure of the strength of interlipid interactions, from "donor" lipid vesicles was determined. This was accomplished using (7-nitrobenzo-2-oxa-1,3-diazole-4-yl)aminohexanoate (C6-NBD) labeled phospholipids, the rate of desorption being followed from changes in fluorescence with time. The rates of desorption of the NBD-phospholipids from phosphatidylcholine (PC) donor vesicles was in the order phosphatidylcholine (PC) > phosphatidylserine (PS) > phosphatidylethanolamine (PE), the slower rates in the PS and PE reflecting direct interlipid hydrogen bonding. For PC, the interlipid hydrogen bonding was restricted to the "hydration layer", the network of hydrogen-bonded water molecules extending between phospholipid head groups. The rate of C6-NBD-PC desorption was elevated with higher levels of donor PC sn-2 unsaturation, due the increased head group spacing weakening the lipid-lipid interactions that occur via the hydration layer. Ethanol also increased the rate of NBD-phospholipid desorption from donor PC vesicles in the order PC > PS > PE, showing that PC interactions, here limited to the weaker hydrogen-bonded water molecule network, were more susceptible compared to stronger, direct interlipid hydrogen bonds involving PE and PS. The relative magnitude of the ethanol-induced increase in the desorption rate was amplified with higher levels of donor lipid sn-2 unsaturation. Cholesterol had little effect on the rate of phospholipid desorption.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Chloro-7-nitrobenzofurazan↗
PubMed1982

Phospholipid molecular species alterations in Tetrahymena ciliary membranes following low-temperature acclimation.

The molecular species compositions of phosphatidylcholine, phosphatidylethanolamine, and 2-(aminoethyl)-phosphonolipid, the three principal phosphoglycerides of Tetrahymena pyriformis ciliary membranes, have been determined by coupled gas chromatography-mass spectrometry of the tert-butyldimethylsilyl derivatives of their phospholipase C derived diglycerides. There were striking changes in the molecular species composition of phosphatidylcholine and phosphatidylethanolamine after the cells were chilled from 39 to 15 degrees C. The low temperature induced changes occurring in each phospholipid class were markedly different from those taking place in the other two. The molecular species patterns of the ciliary phosphoglycerides resembled in a qualitative way the patterns found in their microsomal counterparts. However, the relative proportions of many molecular species within each ciliary phospholipid class were very different from those of the corresponding microsomal component, and changes induced in a particular microsomal phospholipid class by chilling were often absent or even reversed in the equivalent ciliary phospholipid. Compositional changes in ciliary phospholipids during low-temperature acclimation were greater in nearly all respects than were concurrent changes in microsomal phospholipids. The molecular species data confirm that the cell possesses a variety of highly selective mechanisms allowing those organelles which accept phospholipids of microsomal origin to retain a surprising degree of independence in responding to environmental stress.

Acclimatization↗
PubMed1987

Role of substrate in imparting calcium and phospholipid requirements to protein kinase C activation.

The role of substrate in influencing the cofactor requirements of the phospholipid- and Ca2+-dependent protein kinase C (PKC) was investigated by using several substrates. All of the substrates tested, including histone, troponin I, myosin light chain, protamine, poly(arginine, serine) (PAS), poly(lysine, serine) (PLS), and myelin basic protein (MBP), were found to interact with and aggregate phospholipid vesicles as well as phosphatidylserine (PS)-Triton mixed micelles. Phosphorylation of these different substrates by PKC indicated the presence of three distinct substrate categories: substrates such as protamine requiring no cofactors; substrates such as PLS, PAS, and MBP requiring only the presence of phospholipid; and substrates such as histone, myosin light chain, and troponin I requiring the presence of Ca2+ and phospholipid. Diacylglycerol was a major cofactor only with category C substrates. These different requirements correlated with the interaction of the substrate with phospholipid and/or enzyme. The substrates in category A interacted strongly with and aggregated PKC in a binary mixture. In the absence of Ca2+, PKC bound to substrates of category B directly but not to substrates in category C. Thus, substrate-enzyme binding eliminated the Ca2+ requirement of phosphorylation, and aggregation of substrate-enzyme complex eliminated the phospholipid requirements as well. Substrate-phospholipid interaction and substrate phosphorylation were inhibited by increasing salt concentrations, but the amount needed depended upon the substrate. Loss of PKC activity appeared to coincide with loss of substrate-PS aggregation while dissociation of PKC from the membranes required much higher salt concentrations. Poly(L-lysine) and poly(L-arginine), two potent inhibitors of PKC, also showed substrate-dependent inhibition characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Thermal dependence of apolipoprotein A-I-phospholipid recombination.

Studies of the recombination of apolipoprotein A-I (apo A-I), the major protein constituent of human high-density lipoprotein, and various synthetic phospholipids, both alone and in mixtures, have been performed. Pure diacyl phospholipids containing homologous fatty acids of the C12, C13, C14, and C15 series, as well as the two positional isomers containing C14 and C16 fatty acids in positions 1 and 2, undergo reaction with the apo A-I protein only near their gel-liquid-crystalline transition temperatures; the degree of reactivity of these phospholipids toward recombination was observed to decrease as the transition temperature increased. The presence of lysolecithin in the incubation mixtures at proportions of 5 mol/mol of protein or lower was not found to have a significant effect on the rate of recombination. Binary mixtures of dimyristoylphosphatidylcholine and dipalmitoylphosphatidylcholine at various proportions react maximally with apo A-I at the onset of the phase transition, as judged by comparison with published phase diagrams; in this case also, the rate of recombination was observed to decline for mixtures with higher phase transition temperatures. These results are interpreted in terms of protein insertion at lattice defects arising from the presence of phospholipid clusters undergoing the phase transition; these clusters are derived from the cooperative and simultaneous melting of a number of molecules, the cooperativity being dependent upon the nature of the phospholipid. It is postulated that phospholipids which melt in a more highly cooperative fashion are more capable of interacting with the apolipoproteins since these phospholipids will possess larger lattice defects during the phase transition.

Apolipoprotein A-I↗
PubMed1980

Structural role of phospholipids in ubiquinol-cytochrome c reductase.

The role of phospholipids in ubiquinol-cytochrome c reductase has been studied by the following methods: (1) removal and restoration of phospholipids, (2) circular dichroism measurements, and (3) phospholipase A2 treatment. Over 90% of the phospholipids in the cytochrome b--c1 III complex (a highly purified ubiquinol-cytochrome c reductase) can be removed by repeated precipitation with ammonium sulfate in the presence of 0.5% sodium cholate. The delipidated enzyme complex is inactive. Full restoration of enzymatic activity can only be achieved with a freshly prepared delipidated enzyme complex, made in the presence of 20% glycerol. As the age of the delipidated enzyme increased, the amount of activity restored decreased and the incubation time required to reach maximal activity increased. Removal of phospholipids from the cytochrome b--c1 III complex resulted in an immediate decrease of approximately 15% in molar ellipticities in both the far-UV and the Soret regions. A further decrease in ellipticities was observed upon incubation of the delipidated enzyme at 0 degrees C in 50 mM phosphate buffer, pH 7.4. Replenishing phospholipids to the delipidated enzyme complex restored enzymatic activity and the molar ellipticity in both regions. The absolute requirement for phospholipids in the cytochrome b--c1 III complex was also demonstrated by treatment of the enzyme with purified phospholipase A2. The inactivation of the cytochrome b--c1 III complex by phospholipase A2 was not prevented by the presence of excess exogenous ubiquinone but was prevented by the presence of ethylenediaminetetracetic acid (EDTA). The enzymatic activity of the phospholipase A2 treated complex is fully restorable upon the addition of EDTA and phospholipids.

Circular Dichroism↗
PubMed1977

Phospholipid-protein interactions in human low density lipoprotein detected by 31P nuclear magnetic resonance.

31P nuclear magnetic resonance (NMR) spectra of human low density lipoprotein (LDL) has been obtained and the major phospholipid components identified. Analysis of the spectra revealed two phospholipid environments: one occupied by 4/5 of the phospholipid with high resolution resonances possessing properties similar to phospholipids in vesicles, and a second occupied by 1/5 of the phospholipid with broad lines indicative of immobilization. Limited trypsin treatment of the particle cleaved all of the B peptide into smaller molecular weight peptides which remained with the particle. Trypsin-treated LDL eluted from a Sepharose CL-6B column similarly to native LDL so that the modified particle remained intact. 31P NMR spectra of trypsin-treated LDL showed little or no immobilized phospholipid. The immobilization in the native LDL particle is attributed to lipid-protein interactions between 1/5 of the phospholipid and the B peptide.

Apolipoproteins↗
PubMed2001

Calcium-dependent binding of annexin 12 to phospholipid bilayers: stoichiometry and implications.

Annexins (ANXs) are a superfamily of proteins whose functional hallmark is Ca2+-dependent binding to anionic phospholipids. Their core domains are usually composed of a 4-fold repeat of a conserved amino acid sequence, with each repeat containing a type II Ca2+ binding site that is generally thought to mediate Ca2+-dependent binding to the membrane. We now report that ANX12 binding to phospholipid vesicles is highly cooperative with respect to Ca2+ concentration (Hill constant approximately 7), thereby suggesting that more than the four well-characterized type II Ca2+ binding sites are involved in phospholipid binding. Two independent approaches, a novel 45Ca2+ copelleting assay and isothermal titration calorimetry, indicate a stoichiometry of approximately 12 mol of Ca2+/mol of ANX12 for binding to phospholipid vesicles. On the basis of the "low-affinity" Ca2+-binding sites in a number of ANX X-ray crystal structures, we propose a model for ANX12 bilayer binding that involves three types of Ca2+ sites in each of the four repeats. In this model, there is a complementarity between the spacing of the ANX12 Ca2+ binding sites and the spacing of the phospholipid headgroups in bilayers. We tested the implications of the model by manipulating the physical state of vesicles composed of phospholipids with saturated acyl chains with temperature and measuring its influence on ANX12 binding. ANX12 bound to vesicles in a Ca2+-dependent manner when the vesicles were in the liquid crystal phase but not when the phospholipid was in the gel phase. Furthermore, ANX12 bound initially to fluid bilayers remained bound when cooled to 4 degrees C, a temperature that should induce the gel phase transition. Overall, these studies suggest that ANX12 is well suited to being a Ca2+ sensor for rapid all-or-none intercellular membrane-related events.

Animals↗
PubMed2004

Apolipoprotein E enhances hepatic lipase-mediated hydrolysis of reconstituted high-density lipoprotein phospholipid and triacylglycerol in an isoform-dependent manner.

This study compares the kinetics of hepatic lipase (HL)-mediated phospholipid and triacylglycerol hydrolysis in spherical, reconstituted high-density lipoproteins (rHDL) that contain either apolipoprotein E2 (apoE2), apoE3, apoE4, or apoA-I as the sole apolipoprotein. HL-mediated phospholipid hydrolysis was assessed by incubating various concentrations of rHDL that contained only cholesteryl esters (CE) in their core, (E2/CE)rHDL, (E3/CE)rHDL, (E4/CE)rHDL, and (A-I/CE)rHDL, with a constant amount of HL. The rate of phospholipid hydrolysis was determined as the formation of nonesterified fatty acid mass. HL-mediated triacylglycerol hydrolysis was assessed in rHDL containing CE, unlabeled triacylglycerol, and [(3)H]triacylglycerol in their core, (E2/TG)rHDL, (E3/TG)rHDL, (E4/TG)rHDL, and (A-I/TG)rHDL. Triacylglycerol hydrolysis was determined as the ratio of (3)H-labeled hydrolysis products to (3)H-labeled unhydrolyzed triacylglycerol. The rates of phospholipid hydrolysis in the (E2/CE)rHDL, (E3/CE)rHDL, and (E4/CE)rHDL were significantly greater than that in the (A-I/CE)rHDL. The rates of triacylglycerol hydrolysis were also greater in the (E2/TG)rHDL, (E3/TG)rHDL, and (E4/TG)rHDL compared to the (A-I/TG)rHDL, although to a lesser degree than observed with phospholipid hydrolysis. Furthermore, the rates of both phospholipid and triacylglycerol hydrolyses were greater in the (E2)rHDL than in either the (E3)rHDL or the (E4)rHDL. These results show that apoE increases the rate of HL-mediated phospholipid and triacylglycerol hydrolysis in rHDL and that this influence is isoform dependent.

Apolipoproteins E↗
PubMed2004

Caloric restriction results in phospholipid depletion, membrane remodeling, and triacylglycerol accumulation in murine myocardium.

Herein, we utilize the power of shotgun lipidomics to demonstrate that modest caloric restriction results in phospholipid depletion, membrane remodeling, and triacylglycerol (TAG) accumulation in murine myocardium. After brief periods of fasting (4 and 12 h), substantial decreases occurred in the choline and ethanolamine glycerophospholipid pools in murine myocardium (collectively, a decrease of 39 nmol of phospholipid per milligram of protein at 12 h representing approximately 25% of total phospholipid mass and approximately 20 cal of Gibbs free energy per gram wet weight of tissue). Remarkably, the selective loss of long-chain polyunsaturated molecular species was present in the major phospholipid classes thereby altering the physical properties of myocardial membranes. No decrease in TAG mass was present in myocardium during fasting, but rather myocardial TAG increased during 12 h of refeeding nearly 3-fold returning to baseline levels only after 24 h of refeeding. No alterations in other examined lipid classes were present during fasting. In contrast to these lipid alterations in myocardium, no decreases in phospholipid mass were present in skeletal muscle myocytes and a dramatic decrease in skeletal muscle (or skeletal muscle associated) TAG mass was prominent after 12 h of fasting. These results identify phospholipids as a rapidly mobilizable energy source during modest caloric deprivation in murine myocardium, while triacylglycerols are a major source of energy reserve in skeletal muscle. Collectively, these results demonstrate dramatic alterations in the membrane composition of mildly fasted mammalian myocardium that identify the unanticipated plasticity of myocardial phospholipids to adapt to modest chemical and physical perturbations.

Animals↗
PubMed2005

Trans fatty acid derived phospholipids show increased membrane cholesterol and reduced receptor activation as compared to their cis analogs.

The consumption of trans fatty acid (TFA) is linked to the elevation of LDL cholesterol and is considered to be a major health risk factor for coronary heart disease. Despite several decades of extensive research on this subject, the underlying mechanism of how TFA modulates serum cholesterol levels remains elusive. In this study, we examined the molecular interaction of TFA-derived phospholipid with cholesterol and the membrane receptor rhodopsin in model membranes. Rhodopsin is a prototypical member of the G-protein coupled receptor family. It has a well-characterized structure and function and serves as a model membrane receptor in this study. Phospholipid-cholesterol affinity was quantified by measuring cholesterol partition coefficients. Phospholipid-receptor interactions were probed by measuring the level of rhodopsin activation. Our study shows that phospholipid derived from TFA had a higher membrane cholesterol affinity than their cis analogues. TFA phospholipid membranes also exhibited a higher acyl chain packing order, which was indicated by the lower acyl chain packing free volume as determined by DPH fluorescence and the higher transition temperature for rhodopsin thermal denaturation. The level of rhodopsin activation was diminished in TFA phospholipids. Since membrane cholesterol level and membrane receptors are involved in the regulation of cholesterol homeostasis, the combination of higher cholesterol content and reduced receptor activation associated with the presence of TFA-phospholipid could be factors contributing to the elevation of LDL cholesterol.

Animals↗