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At least 1,459 records · Page 81Linked to original sources
PubMed2000

Oligonucleotide delivery by a cationic derivative of the polyene antibiotic amphotericin B. II: study of the interactions of the oligonucleotide/cationic vector complexes with lipid monolayers and lipid unilamellar vesicles.

We report a study of the behavior of oligodeoxyribonucleotide (ODN)/amphotericin B3-(N'-dimethylamino)propylamide (AMA) complexes, in the presence of lipid monolayers and large unilamellar vesicles. This study follows the recent discovery of the capacity of AMA, as a new cationic vector, to enhance ODN cellular uptake and efficacy. It aims at investigating the internalization mode of a nucleic acid by AMA. A first study at the air-water interface of AMA and AMA/ODN by surface pressure measurement shows that only free AMA would adsorb at the air-water interface. Second, in the presence of zwitterionic phospholipid- and sterol-containing mixture, ODN-AMA interactions in solution would be higher than lipid-AMA interactions at the interface. In monolayer or with large unilamellar vesicles, AMA monomers adsorb mainly at the phospholipid interface. These results favor a crossing mechanism through AMA channel formation, despite the size of ODN.

Amphotericin B↗
PubMed2002

Attaching histidine-tagged peptides and proteins to lipid-based carriers through use of metal-ion-chelating lipids.

The therapeutic potential of selected peptides and proteins is enormous, with applications ranging from use as therapeutic vaccines, as modulators of intracellular signaling pathways and as highly selective agents capable of recognizing unique extracellular targets. We have been pursuing development of hybrid lipid-based carrier formulations designed to take advantage of the therapeutic benefits of peptides selected for their ability to act in a complementary fashion with the carrier system. In this regard, it is critical to have simple and versatile methods to promote and control the binding of diverse peptides to a broad range of carrier formulations. As demonstrated here, recombinant proteins and synthetic peptides containing poly-histidine residues (4 to 10) can be specifically bound to liposomes containing a metal-ion-chelating lipid, DOGS-NTA-Ni. The potential of this approach is demonstrated using two functional peptides, AntpHD-Cw3 (applications for vaccine production) and AHNP (specificity for Her-2 expressing cells).

Animals↗
PubMed1996

Lateral diffusion in planar lipid bilayers: a fluorescence recovery after photobleaching investigation of its modulation by lipid composition, cholesterol, or alamethicin content and divalent cations.

In spite of the fact that planar lipid bilayers are still the best-suited artificial membrane system for the study of reconstituted ion channels and receptors, data dealing with their physical characterization, especially as regards dynamics, are scanty. A combined electrical and optical chamber was designed and allowed fluorescence recovery after photobleaching recovery curves to be recorded from stable virtually solvent-free bilayers. D, the lateral diffusion coefficient of N-(7-nitrobenzoyl-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn- glycero-3-phosphoethanolamine, was found to be relatively insensitive to the phospholipid composition (headgroup, chain unsaturation, etc.), whereas inclusion of 33-50% cholesterol in the membrane reduced D by a factor of 2. Divalent cations significantly reduced D of negatively charged bilayers. These results compare well with data gathered on other model and natural systems. In addition, the incorporation of the voltage-dependent pore-former alamethicin did slightly reduce lipid lateral mobility. This study demonstrates the feasibility of such experiments with planar bilayers, which are amenable to physical constraints, and thus offers new opportunities for systematic studies of structure-function relationships in membrane-associating molecules.

Alamethicin↗
PubMed2003

Growth of cationic lipid toward bilayer lipid membrane by solution spreading: scanning probe microscopy study.

The growth of cationic lipid dioctadecyldimethylammonium bromide (DODAB) toward bilayer lipid membrane (BLM) by solution spreading on cleaved mica surface was studied by atomic force microscopy (AFM). Bilayer of DODAB was formed by exposing mica to a solution of DODAB in chloroform and subsequently immersing into potassium chloride solution for film developing. AFM studies showed that at the initial stage of the growth, the adsorbed molecules exhibited the small fractal-like aggregates. These aggregates grew up and expanded laterally into larger patches with time and experienced from monolayer to bilayer, finally a close-packed bilayer film (5.4+/-0.2 nm) was approached. AFM results of the film growth process indicated a growth mechanism of nucleation, growth and coalescence of dense submonolayer, it revealed the direct information about the film morphology and confirmed that solution spreading was an effective technique to prepare a cationic bilayer in a short time.

Aluminum Silicates↗
PubMed2002

Lipid peroxidation in rat brain during focal cerebral ischemia: prevention of malondialdehyde and lipid conjugated diene production by a novel antiepileptic, lamotrigine.

The effects of Lamotrigine (LTG) which blocks ischemia induced glutamate (Glu) release, on lipid peroxidation have been evaluated in cortical and cerebellar tissues of rat brain during focal cerebral ischemia. A total of 45 rats were randomly assigned into one of four groups; sham operated animals as controls, animals subjected to middle cerebral artery occlusion (MCAO) and treatment groups with LTG (20 mg/kg i.p.) either 30 min before or just after MCAO. Changes in lipid peroxides were expressed as nanomoles of malondialdehyde (MDA) and conjugated diene (CD) per milligram of protein. MDA values following 60 min of ischemia relative to contralateral cortex and CD levels in 0, 10 and 60 min of ischemia were found to be higher in the ipsilateral cortex than those in the contralateral cortex. On the other hand, contralateral cerebellar MDA levels after 0 and 60 min of ischemia and CD levels after 0, 10 and 60 min of ischemia were higher than those in the ipsilateral cerebellum. Pharmacological inhibition of Glu release significantly decreased the MDA and CD production in both cortex and cerebellum. Pre- or post-ischemic administration of LTG did not significantly change CD levels, but MDA levels in contralateral cortex were found to be significantly decreased than those in ischemic cortex in both pre- and post-treated group.

Animals↗
PubMed2001

Long-term risk stratification for survivors of acute coronary syndromes. Results from the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Study. LIPID Study Investigators.

OBJECTIVES: We developed a prognostic strategy for quantifying the long-term risk of coronary heart disease (CHD) events in survivors of acute coronary syndromes (ACS). BACKGROUND: Strategies for quantifying long-term risk of CHD events have generally been confined to primary prevention settings. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, which demonstrated that pravastatin reduces CHD events in ACS survivors with a broad range of cholesterol levels, enabled assessment of long-term prognosis in a secondary prevention setting. METHODS: Based on outcomes in 8,557 patients in the LIPID study, a multivariate risk factor model was developed for prediction of CHD death or nonfatal myocardial infarction. Prognostic indexes were developed based on the model, and low-, medium-, high- and very high-risk groups were defined by categorizing the prognostic indexes. RESULTS: In addition to pravastatin treatment, the independently significant risk factors included: total and high density lipoprotein cholesterol, age, gender, smoking status, qualifying ACS, prior coronary revascularization, diabetes mellitus, hypertension and prior stroke. Pravastatin reduced coronary event rates in each risk level, and the relative risk reduction did not vary significantly between risk levels. The predicted five-year coronary event rates ranged from 5% to 19% for those assigned pravastatin and from 6.4% to 23.6% for those assigned placebo. CONCLUSIONS: Long-term prognosis of ACS survivors varied substantially according to conventional risk factor profile. Pravastatin reduced coronary risk within all risk levels; however, absolute risk remained high in treated patients with unfavorable profiles. Our risk stratification strategy enables identification of ACS survivors who remain at very high risk despite statin therapy.

Aged↗
PubMed2004

The role of scavenger receptor class B type I (SR-BI) in lipid trafficking. defining the rules for lipid traders.

The scavenger receptor class B type I (SR-BI) is a 509-amino acid, 82 kDa glycoprotein, with two cytoplasmic C- and N-terminal domains separated by a large extracellular domain. The aim of this review is to define the role of SR-BI as a lipoprotein receptor responsible for selective uptake of cholesteryl esters (CE) from high density lipoprotein (HDL) and low density lipoprotein (LDL) and free cholesterol (FC) efflux to lipoprotein acceptors. These activities depend on lipoprotein binding to its extracellular domain and subsequent lipid exchange at the plasma membrane. CE selective uptake supplies cholesterol to liver and steroidogenic tissues, for biliary cholesterol secretion and steroid hormone synthesis. Genetically modified mice have confirmed SR-BI's major role in tissue cholesterol uptake and in reverse cholesterol transport, i.e. cholesterol turnover. Accordingly, cellular cholesterol level, estrogens and trophic hormones regulate SR-BI expression by both transcriptional and post-transcriptional mechanisms. Importantly, mouse SR-BI overexpression has both corrective and preventive effects on atherosclerosis. Human SR-BI has very similar tissue distribution, binding properties and lipid transfer activities compared to rodent SR-BI. However, human plasma has most of its cholesterol in LDL. Thus, there is considerable interest to develop anti-atherogenic strategies involving human SR-BI-mediated increases in reverse cholesterol transport through HDL and/or LDL.

Amino Acid Sequence↗
PubMed2001

Is the oxidation of high-density lipoprotein lipids different than the oxidation of low-density lipoprotein lipids?

This article gives detailed insight into the kinetics of high-density lipoprotein (HDL) oxidation catalyzed by azobis(2-amidinopropane).dihydrochloride (ABAP) or by copper. ABAP initialized oxidation of human HDL 3-4 times faster than non-human primate HDL with a similar composition. The oxidizability of non-human primate HDL was 1000 times lower than the oxidizability calculated from rate constants derived from liposome oxidation, suggesting that there is a slow step in HDL oxidation not present in liposomes. Saturable binding of copper to HDL was a significant feature of copper-catalyzed oxidation. Binding constants (K(m)) for non-human primate HDL were 2-3-fold lower than those for human HDL. Copper-catalyzed oxidation of non-human primate HDL was slower than that of human HDL, but human HDL(2) and HDL(3) oxidized at about the same rate. Overall, the kinetics describing the oxidation of HDL were mechanistically similar to those reported for LDL, suggesting that HDL lipids were as easily oxidized as LDL lipids and that HDL will be easily oxidized in vivo when exposed to agents that oxidize LDL.

Amidines↗
PubMed1980

Paramagnetic isoprenoid carrier lipids. 2. Dispersion and dynamics in lipid membranes.

The transbilayer diffusion rates and self-association of spin-labeled glycosyl carrier lipids and other isoprenoids have been studied in model phospholipid membranes. Transposition rates of phosphorylated species in small (300 A) or large (greater than or equal to 1000 A) diameter unilamellar phosphatidylcholine (PC) vesicles are slow (t1/2 greater than 5 h at 25 degrees C); this argues against their proposed role in the transbilayer portage of sugar units during polysaccharide and glycoprotein assembly. The same probes mix well with several host lipids, remaining monomolecularly dispersed even at high ionic strength (0.5 M NaCl) or in the presence of various polyvalent cations. This behavior persists for several degrees beneath the transition temperature (Tc) of saturated lecithins. In contrast, neutral carboxylate analogues undergo pronounced reversible self-association. Aggregation is quite dependent on the probe concentration and nature of the host but only weakly temperature dependent above the Tc. Even at low probe concentrations (less than 0.5 mol %) in fluid membranes, aggregates persist above 75 degrees C. Unsaturation in the lecithin fatty acyl chains dramatically increases isoprenoid monomer solubility. Segregation appears to involve relocation of the entire molecule in the membrane interior.

Diffusion↗
PubMed2004

Enthalpy-driven apolipoprotein A-I and lipid bilayer interaction indicating protein penetration upon lipid binding.

The interaction of lipid-free apolipoprotein A-I (apoA-I) with small unilamellar vesicles (SUVs) of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) with and without free cholesterol (FC) was studied by isothermal titration calorimetry and circular dichroism spectroscopy. Parameters reported are the affinity constant (K(a)), the number of protein molecules bound per vesicle (n), enthalpy change (DeltaH degrees), entropy change (DeltaS degrees ), and the heat capacity change (DeltaC(p) degrees). The binding process of apoA-I to SUVs of POPC plus 0-20% (mole) FC was exothermic between 15 and 37 degrees C studied, accompanied by a small negative entropy change, making enthalpy the main driving force of the interaction. The presence of cholesterol in the vesicles increased the binding affinity and the alpha-helix content of apoA-I but lowered the number of apoA-I bound per vesicle and the enthalpy and entropy changes per bound apoA-I. Binding affinity and stoichiometry were essentially invariant of temperature for binding to SUVs of POPC/FC at a molar ratio of 6/1 at (2.8-4) x 10(6) M(-1) and 2.4 apoA-I molecules bound per vesicle or 1.4 x 10(2) phospholipids per bound apoA-I. A plot of DeltaH degrees against temperature displayed a linear behavior, from which the DeltaC(p) degrees per mole of bound apoA-I was calculated to be -2.73 kcal/(mol x K). These results suggested that binding of apoA-I to POPC vesicles is characterized by nonclassical hydrophobic interactions, with alpha-helix formation as the main driving force for the binding to cholesterol-containing vesicles. In addition, comparison to literature data on peptides suggested a cooperativity of the helices in apoA-I in lipid interaction.

Apolipoprotein A-I↗
PubMed1999

Formation of domains of cationic or anionic lipids in binary lipid mixtures increases the electrostatic coupling strength of water-soluble proteins to supported bilayers.

The electrostatic binding strength of water-soluble proteins having either an excess positive (cytochrome c) or negative (beta-lactoglobulin) electric charge to oppositely charged supported planar bilayers (SPBs) was studied as a function of the bilayer phase state (fluid or gel phase) by IR-ATR spectroscopy. The bilayer consisted of mixtures of zwitterionic DEPC with either cationic DMTAP or anionic DMPG. We observed drastic differences in the binding strength of both proteins for the two bilayer phase states, with the gel phase exhibiting a higher binding strength than the fluid phase, under conditions where the two lipid components had different hydrophobic chain lengths resulting in a nonideal mixing behavior. In addition, for beta-lactoglobulin we observed a strong binding to a gel phase SPB comprising DEPC/DMTAP, while raising the temperature of the SPB above the chain melting transition temperature of the mixture resulted in a complete unbinding of the protein. In contrast, for DMPC/DMTAP having the same cationic charge content but no hydrophobic chain mismatch, no phase-dependent coupling strength of the protein to the SPB was observed. Our results suggest that the formation of charge-enriched domains by partial demixing of the bilayer lipids at the transition to the gel state is crucial for modulation of the protein binding strength to the SPB, while the intrinsic charge of the solid support surface is of minor importance.

Animals↗
PubMed2006

Spreading and segregation of lipids in air-stable lipid microarrays.

As a result of heterogeneous spreading of distinct lipids within the same microspots of air-stable lipid microarrays, ganglioside GM1 tends to segregate and thus enrich within the center area of microspots where being predetermined by the quill pin used for array fabrication, as indicated by the binding pattern of fluorescein-cholera toxin subunit B.

Air↗
PubMed2006

In vivo and in vitro lipid peroxidation of arachidonate esters: the effect of fish oil omega-3 lipids on product distribution.

The effect of lipid composition on the distribution of free radical oxidation products derived from arachidonic acid (20:4) esters has been studied in vitro and in vivo. Pro-inflammatory prostaglandin (PG) F2-like compounds, termed F2-isoprostanes (IsoPs), are produced in vivo and in vitro by the free radical-catalyzed peroxidation of arachidonic acid. Controlled free radical oxidation of mixtures of fatty acid esters in vitro showed that the formation of IsoPs from arachidonate is dramatically influenced by the presence of other fatty acid esters in the reaction mixture. Thus, three lipid mixtures containing the same arachidonate concentration but different amounts of other fatty esters (16:0; 18:1; 18:2; 20:5, and 22:6) were oxidized, and the product yields were determined by GC and LC/MS/MS analysis. The yield of F2-IsoP formed after 1 h of oxidation was 18% (based on arachidonate consumed) for mixtures containing arachidonate as the only oxidizable PUFA, but yields of these biologically active compounds dropped to 6% in polyunsaturated fatty acid (PUFA) mixtures typical of those found in tissues of fish oil-fed animals. F2-IsoP levels were also monitored in the livers of mice on diets supplemented with eicosapentaenoic acid (C20:5 omega-3; EPA), the PUFA most abundant in fish oil. While the level of arachidonic acid present in livers was not significantly different from that in control animals, levels of IsoPs in the liver were reduced in the EPA-fed mice compared to those in controls under conditions of oxidative stress (60 +/- 25% reduction, n = 5) or at baseline (48 +/- 14% reduction, n = 5). These results suggest that dietary omega-3 PUFAs may influence the formation of bio-active peroxidation products derived from omega-6 PUFAs by channeling the free radical pathway away from the F2-IsoPs.

Arachidonic Acid↗
PubMed1999

Effect of dietary lipid-lowering drugs upon plasma lipids and egg yolk cholesterol levels of laying hens.

To evaluate the effect of lipid-lowering agents upon egg quality, reproductive performance, plasma lipids, and egg yolk cholesterol levels, 30-week-old Shaver laying hens were fed a basal diet (commercial ration) supplemented with 0.1% probucol (PROB), 0.025% gemfibrozil (GEMF), or lovastatin at 0.0005% (LOV1), 0.001% (LOV2), or 0.0015% (LOV3) for a 12-week experimental period. It was observed that the supplementation of the drugs did not impair albumen and shell quality. Hen performance was not adversely affected. The depression in triglyceride concentrations approached statistical significance only in LOV2 (38.5%), and total cholesterol was significantly depressed in LOV2 (36.0%), LOV3 (36.8%), PROB (29.6%), and GEMF (30.4%) treatments. Egg cholesterol content, expressed per gram of yolk, was significant lowered in LOV1 (7.5%) and LOV3 (12. 7%).

Animals↗
PubMed2003

Serum lipid levels in an Iranian adults population: Tehran Lipid and Glucose Study.

Data from 6246 participants aged 20-64 years (2339 males and 3907 females) in the cross-sectional phase of Tehran Lipid and Glucose Study (February 1999-May 2000) were used to determine distribution of serum lipid levels after 12-14 hour overnight fast. Mean total cholesterol (TC) concentration was 210 mg/dl. TC was significantly greater in females than males, 213 and 206 mg/dl, respectively (p < 0.0001). Thirty-one percent of population had TC values between 200 and 239 and 24% had values of 240 mg/dl or greater. Mean low-density lipoprotein cholesterol (LDL-C) was 129 and 135 mg/dl in males and females, respectively (p < 0.0001). Twenty-seven percent had LDL-C values between 130 and 159 and 23% had values 160 mg/dl or greater. The mean triglycerides (TGs) values were 190 and 162 mg/dl for males and females, respectively (p < 0.0001). The mean high-density lipoprotein cholesterol (HDL-C) was 39 in males and 45 mg/dl in females (p < 0.0001). The results showed higher levels of TC, LDL-C and TGs and slightly lower HDL-C in Tehranian adults than other studies in the industrialized countries.

Adult↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2005

Lipid phosphate phosphatases and lipid phosphate signalling.

Mammalian LPPs (lipid phosphate phosphatases) are integral membrane proteins that belong to a superfamily of lipid phosphatases/phosphotransferases. They have broad substrate specificity in vitro, dephosphorylating PA (phosphatidic acid), S1P (sphingosine 1-phosphate), LPA (lysophosphatidic acid) etc. Their physiological role may include the attenuation of S1P- and LPA-stimulated signalling by virtue of an ecto-activity (i.e. dephosphorylation of extracellular S1P and LPA), thereby limiting the activation of LPA- and S1P-specific G-protein-coupled receptors at the cell surface. However, our recent work suggests that an intracellular action of LPP2 and LPP3 may account for the reduced agonist-stimulated p42/p44 mitogen-activated protein kinase activation of HEK-293 (human embryonic kidney 293) cells. This may involve a reduction in the basal levels of PA and S1P respectively and the presence of an early apoptotic phenotype under conditions of stress (serum deprivation). Additionally, we describe a model whereby LPP2, but not LPP3, may be functionally linked to the phospholipase D1-derived PA-dependent recruitment of sphingosine kinase 1 to the perinuclear compartment. We also consider the potential regulatory mechanisms for LPPs, which may involve oligomerization. Lastly, we highlight many aspects of the LPP biology that remain to be fully defined.

Animals↗
PubMed2006

Are the lipid-modifying effects of fibrates mediated by alterations in plasma lipid transfer activity?

Fenofibrate, a PPAR-alpha (peroxisome-proliferator-activated receptor-alpha) agonist, has been shown to modify plasma lipid and lipoprotein composition and metabolism by a variety of mechanisms. In addition, fenofibrate has been shown to increase the activity of PLTP (phospholipid transfer protein) and to reduce the activity of CETP (cholesteryl ester transfer protein). It is not known, however, whether the changes in PLTP and CETP plasma activity play an active role in the lipid changes observed with fenofibrate therapy, and this is investigated by Watts and co-workers in the present issue of Clinical Science.

Cholesterol Ester Transfer Proteins↗