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At least 253 records · Page 14Linked to original sources
PubMed1996

The effect of high external pressure on DPPC-cholesterol multilamellar vesicles: a pressure-tuning Fourier transform infrared spectroscopy study.

We have investigated the effect of incorporation of cholesterol on the barotropic phase behavior of aqueous dispersions of 1,2-dipalmitoylphosphatidylcholine (DPPC) using Fourier-transform infrared spectroscopy (FTIR) in combination with the diamond anvil technique. Infrared spectral parameters, such as the frequencies, intensities, bandshapes and band splittings have been used to detect structural and dynamical changes upon incorporation of cholesterol into the DPPC bilayer. Analysis of these spectral parameters yields information on conformer population, reorientational fluctuations, interchain interaction, hydrogen bonding, interdigitation packing, and phase transformations of the DPPC/cholesterol mixtures. We present FTIR data of aqueous DPPC dispersions at 0, 10, 20, 30, 40, and 50 mol% cholesterol in the pressure range from 0.001 to 20 kbar at two temperatures, 25 degrees C and 55 degrees C. In addition, comprehensive temperature dependent measurements in the range from 20 degrees C to 80 degrees C were performed at ambient pressure. Analysis of the CH2 symmetric and antisymmetric stretching modes yields information of the effect of cholesterol concentration on the phase transition phenomena occurring in the lipid bilayer. Observation of the correlation field splittings of the CH2 bending and rocking modes monitors structural changes and dynamical properties of the lipid mixtures. Cholesterol induces more orientational disorder of the lipid molecules in terms of an increase of the reorientational fluctuations of the molecules and twisting/torsion motions of the acyl chains in the gel phase even at elevated pressures. It therefore appears that one important role of cholesterol is to make the membrane insensitive to changes in external environment, such as high hydrostatic pressure. Increase of pressure leads to a decrease in half width of the C = O band contour of pure DPPC and of DPPC/cholesterol mixtures, especially for cholesterol concentrations equal and higher than 30 mol%, which might be due to a marked increase in free carbonyl groups. At high pressure part of the bound water from the interfacial zone of the membrane is withdrawn. Increase of the cholesterol concentration and increase in pressure have opposite effects on the population of free and hydrated carbonyl ester groups of DPPC in the gel phases.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

Dynamic partitioning into lipid rafts controls the endo-exocytic cycle of the alphaL/beta2 integrin, LFA-1, during leukocyte chemotaxis.

Cell migration entails the dynamic redistribution of adhesion receptors from the cell rear toward the cell front, where they form new protrusions and adhesions. This process may involve regulated endo-exocytosis of integrins. Here we show that in primary neutrophils unengaged alphaL/beta2 integrin (LFA-1) is internalized and rapidly recycled upon chemoattractant stimulation via a clathrin-independent, cholesterol-sensitive pathway involving dynamic partitioning into detergent-resistant membranes (DRM). Persistent DRM association is required for recycling of the internalized receptor because 1) >90% of endocytosed LFA-1 is associated with DRM, and a large fraction of the internalized receptor colocalizes intracellularly with markers of DRM and the recycling endocytic compartment; 2) a recycling-defective mutant (alphaL/beta2Y735A) dissociates rapidly from DRM upon being endocytosed and is subsequently diverted into a late endosomal pathway; and 3) a dominant negative Rab11 mutant (Rab11S25N) induces intracellular accumulation of endocytosed alphaL/beta2 and prevents its enrichment in chemoattractant-induced lamellipodia. Notably, chemokine-induced migration of neutrophils over immobilized ICAM-1 is abrogated by cholesterol-sequestering agents. We propose that DRM-associated endocytosis allows efficient retrieval of integrins, as they detach from their ligands, followed by polarized recycling to areas of the plasma membrane, such as lamellipodia, where they establish new adhesive interactions and promote outside-in signaling events.

Cells, Cultured↗
PubMedDate not supplied

[The characteristics of changes in lipid metabolism indices of patients with severe mechanical trauma].

The paper contains the study results of some lipid-metabolism indices in patients with severe mechanical injury. Changing concentrations of total cholesterol, triglycerides and of different lipoprotein fractions in blood plasma are demonstrated. It was established that the investigated lipid-metabolism indices reflect a degree of liver malfunction in severely impaired homeostasis. It can be stated on the basis of comparing the study results with the clinical outcome that the dynamic concentration of total cholesterol in blood plasma is an important prognostication factor. Changing ratios of high-density lipoproteins, low-density lipoproteins and extra-low-density lipoproteins were observed in survivors yet by day 15, which is indicative of a commencing dislipidemia.

APACHE↗
PubMed2002

Molecular modelling of membrane sterols with the use of the GROMOS 96 force field.

Membrane located sterols determine the structure and function of eucariotic cell membranes. Moreover, they are targets for important antifungal antibiotic amphotericin B. Knowledge about the geometry and dynamics of sterols in the environment of lipidic membranes is necessary to understand their functions. However, due to the dynamic character of the membrane, no experimental data about sterol behaviour on the molecular level is available. Hence molecular modelling simulations could be a source of useful information. The main goal of this paper is to prove the adequacy of the GROMOS 96 force field for molecular simulations of membrane sterols. We focused our attention on the reproduction of characteristic geometrical features observed in the crystal of cholesterol hemiethanolate by molecular dynamics simulations. The results presented clearly indicate that the GROMOS 96 force field can be a useful tool to simulate the highly lipophilic systems. Moreover, interactions responsible for the stability of such systems can also be recognised.

Cell Membrane↗
PubMed2005

A molecular mechanics force field for biologically important sterols.

A parameterization has been performed of the biologically important sterols cholesterol, ergosterol, and lanosterol for the CHARMM27 all-atom molecular mechanics force field. An automated parameterization method was used that involves fitting the potential to vibrational frequencies and eigenvectors derived from quantum-chemical calculations. The partial charges were derived by fitting point charges to quantum-chemically calculated electrostatic potentials. To model the dynamics of the hydroxyl groups of the sterols correctly, the parameter set was refined to reproduce the energy barrier for the rotation of the hydroxyl group around the carbon connected to the hydroxyl of each sterol. The frequency-matching plots show good agreement between the CHARMM and quantum chemical normal modes. The parameters are tested in a molecular dynamics simulation of the cholesterol crystal structure. The experimental geometry and cell dimensions are well reproduced. The force field derived here is also useful for simulating other sterols such as the phytosterols sigmasterol, and campesterol, and a variety of steroids.

Algorithms↗
PubMed1994

Intramolecular excimer kinetics of fluorescent dipyrenyl lipids: 1. DMPC/cholesterol membranes.

The intramolecular dynamics of the excimer forming dipyrenyl lipids (DipynPC) of different chain lengths (n) in ethanol and in dimyristoylphosphatidycholine (DMPC) membranes was investigated by the use of frequency-domain fluorescence intensity decay technique. Based on a 3-state model, the extent of aggregation and rotational rate of the two intralipid pyrene moieties in the dipyrenyl lipids were estimated from the frequency-domain data. In ethanol (20 degrees C), the rotational rate for DipynPC increased progressively as n was varied from 4 to 12. At the gel (L beta)-to-liquid crystalline (L alpha) phase transition of DMPC (approximately 23 degrees C), the rotational rate increased and aggregation decreased significantly for Dipy10PC, whereas only the rotational rate was changed for Dipy4PC. In the presence of 30 mol% cholesterol, significant increases in both the rotational rate and aggregation were observed for Dipy10PC in both L beta and L alpha phases. However, for the case of Dipy4PC, an increase in the rotational rate but a decrease in the aggregation were noticed only in the L beta phase, and no similar changes were detected in the L alpha phase. Our results indicate differential effects of cholesterol on the conformational dynamics of acyl chains at different depths of the membranes.

Cholesterol↗
PubMed1987

[The effect of beta-carotene on thyroxine and cholesterol levels in pregnant heifers before and after parturition].

Thyroxine (T4) and cholesterol concentrations and their dynamic changes and differences were studied in 20 pregnant heifers 10 days before calving until 56 days after calving. Ten control heifers were fed the feed ration for pregnant heifers according to Czechoslovak Standard CSN 46 7070. The feed ration given to another ten (experimental) heifers was fortified with 300 mg of synthetic beta-carotene per head/day within the period of five months before insemination, during pregnancy and till the 56th day after parturition. As suggested by the regression function of straight line, no obvious differences were recorded in the dynamic changes of T4 before parturition and during the first days after parturition. T4 concentrations had a generally descending tendency in both groups, the lowest values being recorded in the 48th hour in the experimental group and the 24th hour in the control. A marked increase of T4 concentrations with the values significantly higher in the control group than in the experimental group was observed between the 21st and 35th day after calving. A medium increase of cholesterol concentrations was found in the heifers given rations fortified with beta-carotene. No significant differences in cholesterol concentrations were observed between the two groups, except in the 72nd hour and the seventh day. Significant T4: cholesterol correlations were recorded in the experimental animals in the first and second hours, on the 42nd day (P less than 0.05), and in the 72nd hour (P less than 0.001); in the control group these observations were made the seventh day before calving and in the sixth hour and on the 14th, 21st and 56th days (P less than 0.05) after calving. It is inferred from the results that beta-carotene interferes with the activity of the thyroid gland and the production of its hormones, and that the increases or decreases of the activity of this gland, caused by beta-carotene, influence the metabolism of cholesterol in the body.

Animals↗
PubMed1993

[Levels of total lipids, cholesterol and progesterone during estrus synchronization and pregnancy in sheep].

Our investigations were concerned with dynamic changes in total lipids (CL), cholesterol (CHOL) and progesterone (P4) in blood serum of sheep in the period of oestrus synchronization treatment and during mating and gravidity. Our experiment was carried out using 10 animals housed under the conditions of productive rearing. Blood samples were taken from v. jugularis on day of swab application (day 0) and on days 3 and 7 of the action of Agelin vaginal swabs, on day of insemination, and on days 7, 14, 17 and in the 2nd, 3rd and 4th month of gravidity. Blood serum was used to determine total lipids and cholesterol by means of Bio-Lachema tests, and P4 concentrations employing RIA-test-Prog kits (URVJT, Kosice). A statistically significant decrease in concentrations of total lipids (Fig. 1, Tab. I) in sheep blood serum was recorded on day of insemination (P < 0.05) compared to day 0, with the value 1.59 +/- 0.31 g/l of serum, and in the 3rd month of gravidity (P < 0.01), at concentrations 1.36 +/- 0.38 g/l of serum. The determined decrease in their values in the mentioned period can be modulated by the mutually changing ratio of steroid hormones or by inhibition of synthesis of lipoproteins responsible for changes in total plasma lipids. Changes in cholesterol concentrations (Fig. 2, Tab. I) during the introduction of swabs were insignificant and ranged from 1.60 +/- 0.42 to 1.73 +/- 0.33 mmol/l of serum. An insignificant increase in cholesterol concentrations (P < 0.05), with its highest levels 1.98 +/- 0.43 mmol/l of serum, was recorded in the 3rd month of gravidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Serum beta-hexosaminidase and alpha-mannosidase activities as markers of alcohol abuse.

In 25-alcohol-dependent patients in whom detoxication treatment has been introduced serum total beta-hexosaminidase, thermostable beta-hexosaminidase, alpha-mannosidase and gamma glutamylotransferase (GGT) and serum high density lipoprotein (HDL) cholesterol were determined during alcohol withdrawal. The assays were also performed in a group of dependent individuals after a 1 month or longer period of abstinence. Marked increase in beta-hexosaminidase activity was observed in intoxicated patients. The activity decreased rapidly after the cessation of drinking, resembling the decrease in HDL cholesterol level in its dynamics. The alpha-mannosidase activity rise was less pronounced and its normalization was slow, similar to the GGT activity normalization rate. The rise of beta-hexosaminidase activity was mostly due to the thermostable component of the enzyme. Total beta-hexosaminidase or thermostable beta-hexosaminidase activity determinations appear to be simple and reliable markers of alcohol abuse.

Adult↗
PubMed2003

Effects of epicholesterol on the phosphatidylcholine bilayer: a molecular simulation study.

Epicholesterol (Echol) is an epimeric form of cholesterol (Chol). A molecular dynamics simulation of the fully hydrated dimyristoylphosphatidylcholine-Echol (DMPC-Echol) bilayer membrane containing approximately 22 mol % of Echol was carried out for 5 ns. A 3-ns trajectory generated between 2 and 5 ns of molecular dynamics simulation was used for analyses to determine the effects of Echol on the membrane properties. As reference systems, pure DMPC and mixed DMPC-Chol bilayers were used. The study shows that Echol, like Chol, changes the organization of the bilayer/water interface and increases membrane order and condensation, but to a lesser degree. Effects of both sterols are based on the same atomic level mechanisms; their different strength arises from different vertical localizations of Echol and Chol hydroxyl groups in the membrane/water interface.

Cholesterol↗
PubMed2026

Differential regulation of CYP46A1 in ischemic core and peri-infarct regions of male mouse brain after permanent middle cerebral artery occlusion.

Cholesterol 24-hydroxylase (CYP46A1) regulates brain cholesterol homeostasis and synaptic plasticity, playing a crucial role in ischemic stroke. Although previous studies have reported post-ischemic CYP46A1 upregulation, its spatiotemporal dynamics remain poorly defined. To elucidate these dynamics, we investigated the expression of CYP46A1 and other essential cholesterol homeostasis-related genes from 6&#xa0;h to 3&#xa0;days after permanent middle cerebral artery occlusion (pMCAO) in CB-17 mice. We utilized single-cell and single-nucleus transcriptomics, regional quantitative PCR, and high-resolution immunohistochemistry. CYP46A1 is predominantly expressed in neurons. Following ischemia, the cholesterol network exhibited a dynamic spatiotemporal divergence. Acutely (6&#xa0;h post-ischemia), surviving regions transiently upregulated cell-autonomous cholesterol synthesis genes and CYP46A1. Subacutely (3&#xa0;days), this response shifted toward a widespread upregulation of glia-dependent cholesterol transport genes and general CYP46A1 downregulation. At 24&#xa0;h, CYP46A1 protein was substantially reduced in the necrotic core and superficial layer II/III of the peri-infarct cortex, but upregulated in deeper layer V, hippocampus, and lateral striatum. Notably, this localized upregulation spatially coincided with reactive microglial hypertrophy. These findings indicate that CYP46A1 is dynamically modulated in viable tissues following ischemic stress. This spatial divergence likely reflects a synergistic interaction between inflammatory propagation and neural circuit-mediated oxidative stress. Resolving these spatiotemporal profiles provides a rigorous foundation for evaluating CYP46A1 functionality and developing stage-specific therapeutic interventions.

Cholesterol 24-hydroxylase↗
PubMed2004

Interaction of melittin with membrane cholesterol: a fluorescence approach.

We have monitored the organization and dynamics of the hemolytic peptide melittin in membranes containing cholesterol by utilizing the intrinsic fluorescence properties of its functionally important sole tryptophan residue and circular dichroism spectroscopy. The significance of this study is based on the fact that the natural target for melittin is the erythrocyte membrane, which contains high amounts of cholesterol. Our results show that the presence of cholesterol inhibits melittin-induced leakage of lipid vesicles and the extent of inhibition appears to be dependent on the concentration of membrane cholesterol. The presence of cholesterol is also shown to reduce binding of melittin to membranes. Our results show that fluorescence parameters such as intensity, emission maximum, and lifetime of membrane-bound melittin indicate a change in polarity in the immediate vicinity of the tryptophan residue probably due to increased water penetration in presence of cholesterol. This is supported by results from fluorescence quenching experiments using acrylamide as the quencher. Membrane penetration depth analysis by the parallax method shows that the melittin tryptophan is localized at a relatively shallow depth in membranes containing cholesterol. Analysis of energy transfer results using melittin tryptophan (donor) and dehydroergosterol (acceptor) indicates that dehydroergosterol is not randomly distributed and is preferentially localized around the tryptophan residue of membrane-bound melittin, even at the low concentrations used. Taken together, our results are relevant in understanding the interaction of melittin with membranes in general, and with cholesterol-containing membranes in particular, with possible relevance to its interaction with the erythrocyte membrane.

Binding Sites↗
PubMed2003

Redox regulation and signaling lipids in mitochondrial apoptosis.

Apoptosis can be regulated at multiple levels. A number of proteins with regulatory function in cell death are sensitive to cellular redox environment. The antioxidant glutathione (GSH) and redox-sensitive proteins, thioredoxin and glutathione S-transferase, thus regulate cell death pathways by modulating the redox state of specific thiol residues of target proteins including stress kinases, transcription factors, and caspases. GSH in mitochondria plays an important role in the integrity of mitochondrial proteins and lipids known to play a vital role in the permeabilization of mitochondrial membranes and release of proapoptotic factors. The regulation of mitochondrial GSH (mGSH) is determined by its uptake from the cytosol which is dependent on appropriate membrane dynamics. The deposition of cholesterol in mitochondria induced by alcohol intake impairs this translocation, resulting in severe depletion of mGSH and in sensitization to apoptosis stimuli. Although the interaction of proapoptotic proteins with mitochondria initiates apoptotic pathways, recent data indicate that the mitochondrial trafficking of glycosphingolipids, e.g., ganglioside GD3, induced by apoptotic stimuli is a key event that sets off mitochondrial-dependent apoptotic cascades.

Apoptosis↗
PubMed1985

2H NMR evidence for antibiotic-induced cholesterol immobilization in biological model membranes.

The interaction of the polyene antibiotic filipin with membrane sterols has been studied by deuterium nuclear magnetic resonance of the molecular probes [2,2,3,4,4,6-2H6]cholesterol and 1-myristoyl-2-[4',4',14',14',14'-2H5]myristoyl-sn-glycero-3-phospho- choline. At physiological temperatures, there is evidence of filipin-induced cholesterol immobilization in the membrane. The 2H NMR spectra of cholesterol show two domains in which ordering and dynamics are very different. In one of these, cholesterol is static on the 2H NMR time scale, whereas in the other it undergoes rapid axially symmetric motions similar to those it exhibits in the drug-free membrane; this indicates that the jumping frequency of cholesterol between the labile and immobilized domains is less than 10(5) s-1. The distribution of cholesterol between these two sites is temperature dependent; at 0 degrees C all sterol molecules are immobilized, whereas at 60 degrees C they are almost totally in the labile site. In contrast to cholesterol, the phospholipids sense only one type of environment, at both the top and center of the bilayer, indicating that cholesterol acts as a screen, preventing the lipids from direct interaction with the antibiotic. At low temperature, the ordering of the lipid in the presence of cholesterol does not change upon filipin addition, whereas at elevated temperatures the local ordering of both the lipid and the labile cholesterol is significantly lower than that in the absence of the drug. Moreover, there is a very important difference between the degree of local ordering as measured by the lipids and by cholesterol at high temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗
PubMed2000

Annexins in cell membrane dynamics. Ca(2+)-regulated association of lipid microdomains.

The sarcolemma of smooth muscle cells is composed of alternating stiff actin-binding, and flexible caveolar domains. In addition to these stable macrodomains, the plasma membrane contains dynamic glycosphingolipid- and cholesterol-enriched microdomains, which act as sorting posts for specific proteins and are involved in membrane trafficking and signal transduction. We demonstrate that these lipid rafts are neither periodically organized nor exclusively confined to the actin attachment sites or caveolar regions. Changes in the Ca(2+) concentration that are affected during smooth muscle contraction lead to important structural rearrangements within the sarcolemma, which can be attributed to members of the annexin protein family. We show that the associations of annexins II, V, and VI with smooth muscle microsomal membranes exhibit a high degree of Ca(2+) sensitivity, and that the extraction of annexins II and VI by detergent is prevented by elevated Ca(2+) concentrations. Annexin VI participates in the formation of a reversible, membrane-cytoskeleton complex (Babiychuk, E.B., R.J. Palstra, J. Schaller, U. Kämpfer, and A. Draeger. 1999. J. Biol. Chem. 274:35191-35195). Annexin II promotes the Ca(2+)-dependent association of lipid raft microdomains, whereas annexin V interacts with glycerophospholipid microcompartments. These interactions bring about a new configuration of membrane-bound constituents, with potentially important consequences for signaling events and Ca(2+) flux.

Annexin A2↗
PubMed2005

Regulation of human hepatic hydroxysteroid sulfotransferase gene expression by the peroxisome proliferator-activated receptor alpha transcription factor.

Human hydroxysteroid sulfotransferase or (HUMAN)SULT2A1 catalyzes the sulfonation of procarcinogen xenobiotics, hydroxysteroids, and bile acids and plays a dynamic role in hepatic cholesterol homeostasis. The treatment of primary cultured human hepatocytes with a peroxisome proliferator-activated receptor alpha (PPARalpha)-activating concentration of ciprofibrate (10(-) (4) M) increased (HUMAN)SULT2A1 mRNA, immunoreactive protein, and enzymatic activity levels by approximately 2-fold. By contrast, expression of (RAT)SULT2A3, the rat counterpart to (HUMAN)SULT2A1, was induced by treatment of primary hepatocyte cultures with an activator of the pregnane X receptor, but not PPARalpha. In HepG2 cells, transient transfection analyses of luciferase reporter constructs containing upstream regions of the (HUMAN)SULT2A1 gene implicated a candidate peroxisome proliferator response element (PPRE) at nucleotides (nt) -5949 to -5929 relative to the transcription start site. Site-directed mutagenesis and electrophoretic mobility shift assay studies confirmed that this distal PPRE (dPPRE), a direct repeat nuclear receptor motif containing one intervening nt, represented a functional PPRE. Chromatin immunoprecipitation analysis indicated that the (HUMAN)SULT2A1 dPPRE was also a functional element in the context of the human genome. These data support a major role for the PPARalpha transcription factor in the regulation of hepatic (HUMAN)SULT2A1. Results also indicate that important species differences govern the transactivation of SULT2A gene transcription by nuclear receptors.

Animals↗