[Dynamics of blood catalase and peroxidase activity of rabbits during prolonged cholesterol feeding].
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Animals↗
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Results for “Cholesterol dynamics”
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[The dynamic interactions of the level of blood plasma and erythrocyte membrane cholesterol under the influence of the laser irradiation of patients with ischemic heart disease].
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Cholesterol↗
Cytoplasmic proteins, association with phospholipid vesicles and its dependency on cholesterol.
Since the plasticity of the plasma membrane is correlated with changes in its dynamic behavior and biological functions, the content of cholesterol in this membrane is thought to have an important role in the regulation of cell metabolism. The research reported here was done to clarify the role of cholesterol in the interaction of the innersurface of plasma membrane with cytoplasmic proteins in relation to the regulatory mechanism of signal transduction. Many cytoplasmic proteins of EATC or rat liver cells were found to associate with DPPC liposomes and they induced a transient increase in membrane permeability at the phase transition temperature of the liposomal lipid. The association and the permeability increase were inhibited by the introduction of cholesterol into DPPC liposomes, and the sensitivity of individual proteins to the action of cholesterol differed. F-actin, but not G-actin, associated selectively with the liposomes. Also, the main endothermic peak of the unilamellar DPPC liposomes was shifted from 37 degrees C to 43 degrees C by this protein association, evidence of transformation from a unito multilamellar structure. The introduction of cholesterol into the liposomal membrane caused a reduction in the energy content of the phase transition and in the inhibition of protein-membrane interaction. We concluded that the cholesterol in the plasma membrane contributes to the regulation of cell surface signal transduction.
1,2-Dipalmitoylphosphatidylcholine↗
The effects of cholesterol on magnetically aligned phospholipid bilayers: a solid-state NMR and EPR spectroscopy study.
This paper presents the first time that both solid-state NMR spectroscopy and EPR spectroscopy are used to study the effects of cholesterol on magnetically aligned phospholipid bilayers (bicelles). Solid-state deuterium NMR spectroscopy was carried out using both chain perdeuterated 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC-d(54)) and a partially deuterated beta-[2,2,3,4,4,6-(2)H(6)]cholesterol (cholesterol-d(6)). Also, EPR spectroscopy was carried out utilizing a 3 beta-doxyl-5 alpha-cholestane (cholestane) spin probe incorporated into magnetically aligned bilayers to provide a more complete picture about the ordering and dynamics of the phospholipid and cholesterol molecules in the bicelle membrane system. The results demonstrate that cholesterol was successfully incorporated into the phospholipid bilayers. The molecular order parameters extracted directly from the (2)H NMR spectra of both DMPC-d(54) and cholesterol-d(6) were compared to that from the EPR study of cholestane. The order parameters indicate that the sterol was motionally restricted, and that the DMPC had high order and low motion for the hydrocarbon segments close to the head groups of the phospholipids and less order and more rapid motion toward the terminal methyl groups. Both methods clearly indicate an overall increase in the degree of ordering of the molecules in the presence of cholesterol and a decrease in the degree of ordering at higher temperatures. However, EPR spectroscopy and (2)H NMR spectroscopy exhibit different degrees of sensitivity in detecting the phospholipid molecular motions in the membrane. Finally, cholesterol increases the minimum alignment temperature necessary to magnetically align the phospholipid bilayers.
Dimyristoylphosphatidylcholine↗
[Haemodynamic changes and clinic significance in primary pigmentary degeneration of retina].
In comparison with 40 healthy controls, the blood viscosity and erythrocystic agglutination index were predominantly higher in 44 cases with primary pigmentary degeneration. It is believed that the changes mentioned above may result in general and local circulatory disturbance, leading the tissue to ischeia, anoxia and a series of other pathological changes; and exacerbating the functional damage of retina. The author suggests that primary pigmentary degeneration of retina may be treated with the drugs which can lower the blood viscosity, the concentration of blood cholesterol and lipid, and increase blood-dynamics.
Adult↗
[Hypoalphacholesterolemia: dynamics of the subfractional spectrum of high density lipoproteins during their interaction with fibroblasts and hepatoma Hep-G2 cell line].
Using gradient gel electrophoresis, the dynamics of subfractional spectrum of high density lipoproteins (HDL) according to the particle size was studied during HDL interaction with hepatoma Hep-G2 cells and human skin fibroblasts. It was found that incubation of sera obtained from normolipidemic donors with cholesterol-loaded fibroblasts results in a decrease of the proportion of all small-sized particles of the HDL3 subclass, i.e., HDL3a, HDL3b and HDL3c as well as in an increase in the proportion of large-sized particles of the HDL2 subclass (HDL2a and HDL2b) due to cholesterol acceptance by HDL. In contrast, incubation of the same sera with hepatoma Hep-G2 cells causes a decrease in the proportion of HDL2b and a release of smaller cholesterol-deficient HDL3a particles. The dynamics of subfractional spectrum of HDL in hypoalphacholesterolemic sera is somewhat different, i.e., incubation with fibroblasts results in a decrease of the proportion of HDL3b and HDL3c; that of HDL2a is increased. The HDL2b fraction is unchanged. After incubation of the same sera with hepatoma Hep-G2 cells, the proportion of HDL2b does not fall as in the case of normolipidemic sera, but shows a marked increase. It is concluded that hypoalphacholesterolemia is characterized not only by a low HDL level in the plasma, but also by the formation of HDL2b-deficient particles which less effectively interact with liver cells.
Adult↗
The role of the renin-angiotensin system in cholesterol and puromycin mediated renal injury.
BACKGROUND: Puromycin aminonucleoside (PAN) nephropathy is a widely studied model of glomerular sclerosis (GS) in the rat, and cholesterol feeding exacerbates the injury induced by PAN. The importance of the interaction of angiotensin II (Ang II) with the AT2 receptor is unclear. We investigated the role of the renin-angiotensin system, particularly with regard to AT1 and AT2 receptor dynamics, in PAN and cholesterol-mediated GS. METHODS: Sprague-Dawley rats were given a 4% cholesterol diet (group II), subcutaneous PAN (group III), or a 4% cholesterol diet and PAN (group IV) and compared with a control group given PAN vehicle (group I). After 16 weeks, kidneys were harvested and tissue Ang II concentration, angiotensin-converting enzyme (ACE) activity, and ACE, AT1, and AT2 mRNA levels were determined. RESULTS: Compared with control rats, proteinuria was significantly higher in groups II to IV. Kidney ACE activity and ACE mRNA levels in groups III and IV were 2- and 3-fold higher than in groups I and II, respectively. Kidney Ang II concentration also was increased in the experimental groups. Whereas kidney AT1 mRNA was significantly lower in groups III and IV, kidney AT2 mRNA was significantly increased in groups II to IV. CONCLUSION: In these experimental models of GS, there is significant activation of the tissue-based renin-angiotensin system. Puromycin with and without cholesterol decreased the AT1 receptor mRNA and increased the AT2 receptor mRNA. Up-regulation of AT2 receptors may be important in ameliorating the proliferative effects of Ang II, which presumably occur through the AT1 receptor.
Angiotensin II↗
NMDA receptors are not alone: dynamic regulation of NMDA receptor structure and function by neuregulins and transient cholesterol-rich membrane domains leads to disease-specific nuances of glutamate-signalling.
Glutamate receptors of the N-methyl-D-asparate (NMDA-) subtype are tetrameric allosteric and ligand-gated calcium channels. They are modulated by a variety of endogenous ligands and ions and play a pivotal role in memory-related signal transduction due to a voltage-dependent block by magnesium, which makes them Hebbian coincidence detectors. On the structural level NMDA receptors have an enormous flexibility due to seven genes (NR1, NR2A-D and NR3A-B), alternative splicing, RNA-editing and extensive posttranslational modifications, like phosphorylation and glycosylation. NMDA receptors are thought to be responsible for excitotoxicity and subsequent downstream events like neuroinflammation and apoptosis and thus have been implicated in many important human pathologies, ranging from amyotrophic lateral sclerosis, Alzheimer's and Parkinson' disease, depression, epilepsy, trauma and stroke to schizophrenia. This fundamental significance of NMDA receptor-related excitotoxicity is discussed in the context of the developing clinical success of Memantine, but moreover set into relation to various proteomic and genetic markers of said diseases. The very complex localisational and functional regulation of NMDA receptors appears to be dependent on neuregulins and receptor tyrosine kinases in cholesterol-rich membrane domains (lipid rafts), calcium-related mitochondrial feedback-loops and subsynaptic structural elements like PSD-95 (post-synaptic density protein of 95 kD). The flexibility and multitude of interaction partners and possibilities of these highly dynamic molecular systems are discussed in terms of drug development strategies, in particular comparing high affinity and sub-type specific ligands to currently successful or promising therapies.
Alternative Splicing↗
Modulating membrane properties: the effect of trehalose and cholesterol on a phospholipid bilayer.
The protective properties of trehalose on cholesterol-containing lipid dipalmitoylphosphatidylcholine (DPPC) bilayers are studied through molecular simulations. The ability of the disaccharide to interact with the phospholipid headgroups and stabilize the membrane persists even at high cholesterol concentrations and restricts some of the changes to the structure that would otherwise be imposed by cholesterol molecules. Predictions of bilayer properties such as area per lipid, tail ordering, and chain conformation support the notion that the disaccharide decreases the main melting transition in these multicomponent model membranes, which correspond more closely to common biological systems than pure bilayers. Molecular simulations indicate that the membrane dynamics are slowed considerably by the presence of trehalose, indicating that high sugar concentrations would serve to avert possible phase separations that could arise in mixed phospholipid systems. Various time correlation functions suggest that the character of the modifications in lipid dynamics induced by trehalose and cholesterol is different in the hydrophilic and hydrophobic regions of the membrane.
1,2-Dipalmitoylphosphatidylcholine↗
Orientation and dynamics of melittin in membranes of varying composition utilizing NBD fluorescence.
Melittin is a cationic hemolytic peptide isolated from the European honey bee, Apis mellifera. The organization of membrane-bound melittin has earlier been shown to be dependent on the physical state and composition of membranes. In this study, we covalently labeled the N-terminal (Gly-1) and Lys-7 of melittin with an environment-sensitive fluorescent probe, the NBD group, to monitor the influence of negatively charged lipids and cholesterol on the organization and dynamics of membrane-bound melittin. Our results show that the NBD group of melittin labeled at its N-terminal end does not exhibit red edge excitation shift in DOPC and DOPC/DOPG membranes, whereas the NBD group of melittin labeled at Lys-7 exhibits REES of approximately 8 nm. This could be attributed to difference in membrane microenvironment experienced by the NBD groups in these analogs. Interestingly, the membrane environment of the NBD groups is sensitive to the presence of cholesterol, which is supported by time-resolved fluorescence measurements. Importantly, the orientation of melittin is found to be parallel to the membrane surface as determined by membrane penetration depth analysis using the parallax method in all cases. Our results constitute the first report to our knowledge describing the orientation of melittin in cholesterol-containing membranes. These results assume significance in the overall context of the role of membrane lipids in the orientation and function of membrane proteins and peptides.
Amino Acid Sequence↗
Cholesterol-dependent lipid assemblies regulate the activity of the ecto-nucleotidase CD39.
CD39 (ecto-nucleoside triphosphate diphosphohydrolase-1; E-NTPDase1) is a plasma membrane ecto-enzyme that regulates purinergic receptor signaling by controlling the levels of extracellular nucleotides. In blood vessels this enzyme exhibits a thromboregulatory role through the control of platelet aggregation. CD39 is localized in caveolae, which are plasma membrane invaginations with distinct lipid composition, similar to dynamic lipid microdomains, called rafts. Cholesterol is enriched together with sphingolipids in both rafts and caveolae, as well as in other specialized domains of the membrane, and plays a key role in their function. Here, we examine the potential role of cholesterol-enriched domains in CD39 function. Using polarized Madin-Darby canine kidney (MDCK) cells and caveolin-1 gene-disrupted mice, we show that caveolae are not essential either for the enzymatic activity of CD39 or for its targeting to plasma membrane. On the other hand, flotation experiments using detergent-free or detergent-based approaches indicate that CD39 associates, at least in part, with distinct lipid assemblies. In the apical membrane of MDCK cells, which lacks caveolae, CD39 is localized in microvilli, which are also cholesterol and raft-dependent membrane domains. Interfering with cholesterol levels using drugs that either deplete or sequester membrane cholesterol results in a strong inhibition of the enzymatic and anti-platelet activity of CD39. The effects of cholesterol depletion are completely reversed by replenishment of membranes with pure cholesterol, but not by cholestenone. These data suggest a functional link between the localization of CD39 in cholesterol-rich domains of the membrane and its role in thromboregulation.
Actins↗
Effect of cholesterol on DMPC phospholipid membranes and QSAR model construction in membrane-interaction QSAR study through molecular dynamics simulation.
In this study, both pure DMPC and DMPC/cholesterol mixed membrane monolayer were built to compare the physical-chemical properties and dynamics properties through molecular dynamics simulation and normal-mode analysis. The results show that the addition of cholesterol decreases the area of per molecule of membrane, increases the lipid amplitude motion, and changes the solute diffusion coefficient. It is also found that the addition of cholesterol greatly changes the solute-membrane 1,4-nonbonded interaction energy (deltaE14). MI-QSAR models were constructed based on solute-membrane interaction energy descriptors and other intramolecular descriptors. The results show that deltaE14 substitutes deltaE(HB) as the second important descriptor compared with the previous study. Final results suggest that short range solute-membrane interaction energy changes due to the uptake of the solute may play an important decision on permeability in DMPC/cholesterol membrane. A test set was applied to evaluate the predictivity of MI-QSAR models. The result suggests that the combination of F(H2O) and deltaE14 not only improves r2 and q2, but also greatly improves the model predictivity. Based on the combination of q2 and r(pre)2 values, a two-term model is better used to predict the solute permeability in this study (r2 = 0.859, q2 = 0.803, and r(pre)2 = 0.540). Due to the small sample both in training set and test set, more datasets are necessary to make a final decision about the model construction and prediction.
Chemical Phenomena↗
Depletion of cellular cholesterol and lipid rafts increases shedding of CD30.
CD30, a lymphoid activation marker, is shed into the cell environment after endoproteolytic cleavage of its ectodomain. Soluble (s)CD30 is able to suppress the Th1-type immune response. Because high serum levels of sCD30 and cholesterol-lowering drugs seem to be beneficial in some Th1-type autoimmune diseases, we focused on a link between CD30 shedding and the amount of cellular cholesterol. Cholesterol depletion of human Hodgkin lymphoma- and non-Hodgkin lymphoma-derived cell lines by methyl-beta-cyclodextrin led to a down-regulation of membrane-bound CD30 and increased release of sCD30. Additionally, the cholesterol-interfering drugs lovastatin, cholesterol oxidase, and filipin increased CD30 shedding. Both the down-regulation of membrane-anchored CD30 and the release of sCD30 were dependent on metalloproteinases. Using specific inhibitors, we detected TNF-alpha converting enzyme (TACE) as the leading enzyme responsible for cholesterol-dependent CD30 shedding. A Triton X-100-based method for lipid raft isolation revealed that CD30 was partially present in lipid rafts, whereas TACE was localized in the nonraft fractions. Disintegration of lipid rafts by cholesterol depletion might therefore lead to dynamic interactions of CD30 with TACE, resulting in enhanced shedding of CD30. Our results suggest a possible role of cholesterol-dependent shedding of CD30 in the pathogenesis of immune diseases.
ADAM Proteins↗
[Thyroid hormones, cholesterol, erythrocyte aggregation and fibrinogen degradation products in acute myocardial infarct].
One hundred and sixty-two patients with acute myocardial infarction, whose ages ranged from 36 to 65, were studied. The content of thyroid hormones was found to be reduced in the acute period of myocardial infarction. The triiodothyronine level was lower on the 2nd day of the disease, the thyroxine content decreased on the 10th day of the disease but became normal on the 20-25th day. An interrelation between the clinical course of the disease and the dynamics of changes in the cholesterol content, rate of erythrocyte aggregation, the content of fibrinogen degradation products, and the level of thyroid hormones was determined. Normalization of the values was determined. Normalization of the values studied occurred earlier in the group of patients with a more favourable course of the acute period of myocardial infarction than in those with severe myocardial infarction. The data obtained show a close interrelation between thyroid activity and values studied and the clinical course of the disease.
Adult↗
Differential lipid packing abilities and dynamics in giant unilamellar vesicles composed of short-chain saturated glycerol-phospholipids, sphingomyelin and cholesterol.
The ability of membrane components to arrange themselves heterogeneously within the bilayer induces the formation of microdomains. Much work has been devoted to mimicking domain-assembly in artificial bilayers and characterizing their physico-chemical properties. Ternary lipid mixtures composed of unsaturated phospholipids, sphingomyelin and cholesterol give rise to large, round domains. Here, we replaced the unsaturated phospholipid in the ternary mixture with sphingomyelin and cholesterol by saturated glycero-phospholipids of different chain length and characterized the critical role of cholesterol in sorting these lipids by confocal imaging and fluorescence correlation spectroscopy (FCS). More cholesterol is needed to obtain phase segregation in ternary mixtures, in which the unsaturated phospholipid is replaced by a saturated one. Finally, lipid dynamics in distinct phases is very low and astonishingly similar, thereby suggesting the poor ability of cholesterol in sorting short-chain saturated glycero-phospholipids and sphingomyelin.
Cholesterol↗
Lipid rafts and regulation of the cytoskeleton during T cell activation.
The ability of polarized cells to initiate and sustain directional responses to extracellular signals is critically dependent on direct communication between spatially organized signalling modules in the membrane and the underlying cytoskeleton. Pioneering work in T cells has shown that the assembly of signalling modules critically depends on the functional compartmentalization of membrane lipids into ordered microdomains or lipid rafts. The significance of rafts in T cell activation lies not only in their ability to recruit the signalling partners that eventually assemble into a mature immunological synapse but also in their ability to regulate actin dynamics and recruit cytoskeletal associated proteins, thereby achieving the structural polarization underlying stability of the synapse-a critical prerequisite for activation to be sustained. Lipid rafts vary quite considerably in size and visualizing the smallest of them in vivo has been challenging. Nonetheless it is now been shown quite convincingly that a surprisingly large proportion-in the order of 50%-of external membrane lipids (chiefly cholesterol and glycosphingolipids) can be dynamically localized in these liquid ordered rafts. Complementary inner leaflet rafts are less well characterized, but contain phosphoinositides as an important functional component that is crucial for regulating the behaviour of the actin cytoskeleton. This paper provides an overview of the interdependency between signalling and cytoskeletal polarization, and in particular considers how regulation of the cytoskeleton plays a crucial role in the consolidation of rafts and their stabilization into the immunological synapse.
Actins↗
Lateral organization in lipid-cholesterol mixed bilayers.
Interactions between lipid and cholesterol molecules in membranes play an important role in the structural and functional properties of cell membranes. Although structural properties of lipid-cholesterol mixtures have been extensively studied, an understanding of the role of cholesterol in the lateral organization of bilayers has been elusive. In this article, we propose a simple yet powerful model, based on self-consistent mean-field theory and molecular dynamics simulations, for lipid bilayers containing cholesterol. Properties predicted by our model are shown to be in excellent agreement with experimental data. Our model predicts that cholesterol induces structural changes in the bilayer through the formation of regions of ordered lipids surrounding each cholesterol molecule. We find that the "smooth" and "rough" sides of cholesterol play crucial roles in formation and distribution of the ordered regions. Our model is predictive in that input parameters are obtained from independent atomistic molecular dynamics simulations. The model and method are general enough to describe other heterogeneous lipid bilayers, including lipid rafts.
Cholesterol↗
Formation of intranuclear crystalloids and proliferation of the smooth endoplasmic reticulum in schwann cells induced by tellurium treatment: association with overexpression of HMG CoA reductase and HMG CoA synthase mRNA.
Administration of tellurium (Te) in weaning rats causes a well-established demyelinating neuropathy induced by the inhibition in myelinating Schwann cells (SC) of the synthesis of cholesterol, a major component of the myelin sheath, at the level of squalene epoxidase. We have used this experimental model of Te neuropathy to study the biogenesis and reorganization of the endomembranes of the nuclear envelope and endoplasmic reticulum (ER) in response to Te treatment by ultrastructural analysis and in situ hybridization for the detection of HMG CoA reductase and synthase mRNA, which encode key enzymes in cholesterol synthesis. The adaptive response of myelinating SC to cholesterol depletion includes cell hypertrophy, the formation of tubular invaginations of proliferating nuclear membranes giving rise to peculiar nuclear inclusions termed crystalloids, and, at the cytoplasmic level, the formation of lamellar bodies of rough ER, proliferation of the smooth ER, and overexpression of HMG CoA reductase and synthase mRNAs. The changes revert after withdrawal of Te treatment. Our results show that the biogenesis and structural organization of both endomembrane systems change dynamically upon Te-induced cholesterol depletion, indicating that this constituent plays a critical role in the organization of nuclear envelope and ER compartments in SC. The results also suggest that the HMG CoA reductase, an integral membrane protein of ER, provides the signal for the extensive membrane assembly. While the physiological meaning of crystalloid remains to be clarified, the hypertrophy of the smooth ER may represent a cytoprotective mechanism involved in detoxification of the neurotoxic agent or its metabolic derivates.
Animals↗