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At least 919 records · Page 51Linked to original sources
PubMed2007

A spontaneously immortalized Schwann cell line to study the molecular aspects of metachromatic leukodystrophy.

The arylsulfatase A (ASA)-deficient mouse is a murine model of human metachromatic leukodystrophy (MLD) caused by a genetic defect in the ASA gene. Deficiency of ASA causes accumulation of cerebroside-3-sulfate (sulfatide) in visceral organs and in the central and peripheral nervous system, which subsequently causes demyelination in these areas. To investigate further the cellular pathomechanism of MLD, we established spontaneously immortalized Schwann cell lines from ASA-deficient mice. Cells showed marked sulfatide storage in the late endosomal/lysosomal compartment. This sulfatide accumulation can be further increased by external treatment with sulfatide using a lipid based transfection reagent as a cargo. The accumulated sulfatide was degraded in response to ASA treatment and first examination revealed that alteration on the molecular level found in ASA-deficient mice can also be observed in the presented cell culture model. Hence, these cells could be a suitable model to study MLD at a molecular level.

Animals↗
PubMed1980

Retinal pigment epithelial degeneration associated with leukocytic arylsulfatase A deficiency.

A family exhibiting a leukocytic arylsulfatase A deficiency, probably inherited in an autosomal recessive manner, differed from patients with typical metachromatic leukodystrophy in that sulfatiduria was absent and there was readily detectable cerebroside sulfatase activity. To our knowledge, this family was unique in that there were no known members with metachromatic leukodystrophy and the only neurologic abnormality was progressive retinal pigment degeneration in the proband.

Adolescent↗
PubMed1984

Interaction of cholesterol with galactocerebroside and galactocerebroside-phosphatidylcholine bilayer membranes.

The interaction of the galactocerebroside, N-palmitoylgalactosylsphingosine (NPGS), with cholesterol has been studied by differential scanning calorimetry (DSC) and x-ray diffraction. Thermal and structural studies demonstrate complex behavior characterized by two endothermic transitions: transition I (TI approximately equal to 50-60 degrees C) corresponding to an NPGS-cholesterol bilayer gel----bilayer liquid crystal transition II (TII where TI less than TII less than TNPGS) corresponding to an NPGS bilayer crystal (stable E form)----bilayer liquid crystal transition. For mixtures containing from 6 to 80 mol % cholesterol, x-ray diffraction studies at 22 degrees C (T less than TI) indicate two separate lamellar phases; an NPGS crystal bilayer phase and a cholesterol monohydrate phase. For cholesterol concentrations less than 50 mol % at TI less than T less than TII, NPGS-cholesterol liquid crystal bilayer and excess NPGS crystal bilayer phases are observed. For greater than 50 mol % cholesterol concentrations at these temperatures, an excess cholesterol monohydrate phase coexists with the NPGS-cholesterol liquid crystal bilayers. At T greater than TII, complete NPGS-cholesterol miscibility is only observed for less than 50 mol % cholesterol concentrations, whereas at greater than 50 mol % cholesterol an excess cholesterol phase is present. The solid phase immiscibility of cerebroside and cholesterol at low temperatures is suggested to result from preferential NPGS-NPGS associations via hydrogen bonding. The unique thermal and structural behavior of NPGS-cholesterol dispersions is contrasted with the behavior of cholesterol-phosphatidycholine and cholesterol-sphingomyelin bilayers. Thermal and structural studies of NPGS in dipalmitoylphosphatidylcholine (DPPC)/cholesterol (1:1, molar ratio) bilayers have been performed. For dispersions containing less than 20 mol % NPGS at 22 degrees C there are no observable calorimetric transitions and x-ray diffraction studies indicate complete lipid miscibility. At greater than 20 mol % NPGS, a high temperature transition is observed that is shown by x-ray diffraction studies to be due to an excess NPGS crystal bilayer----liquid crystal bilayer transition. Complete miscibility of NPGS in DPPC/cholesterol bilayers is observed at T greater than TNPGS. The properties of NPGS/DPPC/cholesterol bilayers are discussed in terms of the lipid composition of the myelin sheath.

Animals↗
PubMed1978

Myelin lipids in the brain after transplacental intoxication with ethylnitrosourea.

At day 15 of gestation pregnant mice were injected with a single intravenous dose of ethylnitrosourea (ENU) (80 mg/kg of body weight). The lipid composition of the myelin fraction isolated by means of differential centrifugation from brains of their offsprings was studied. The transplacentally intoxicated mice developed severe changes in the lipid composition of their central myelin sheaths, such as a markedly decreased galactolipid (both cerebroside and sulfatide) as well as plasmalogen contents. The results show, that besides being a well known carcinogenic agent, ENU is capable of affecting the lipid metabolism of the developing central nervous system. The resultant effect is the formation of a chemically defective myelin sheath.

Animals↗
PubMed1976

Mouse brain uptake and metabolism of stearic acid.

After injection, labelled stearic acid is transported directly into the brain and incorporated into brain lipids without prior oxydation to acetate and resynthesis of fatty acids. Contamination by blood can be excluded. (The preparation contains all subcellular fraction except cytosol). The labelled stearic acid taken up is partly metabolized in the brain either by elongation or by degradation and in situ resynthesis of fatty acids. The activity in oleic acid and mono-unsaturated chains is hardly detectable. The labelled acids are incorporated into lipids or subcellular particles following characteristic kinetics, which show a diminution by 24 hours. When analysing the evolution of each lipid, it is shown that this profile is followed by phospholipids, but not by cerebrosides and free fatty acids. The formers are still increasing up to 50 hours, the latters are stable (suggesting a physical binding between membranes and free fatty acids). Thus nutrition is an important parameter for the synthesis of brain membranes as far as exogenous saturated fatty acids are needed.

Animals↗
PubMed1987

Brain development in relation to fetal weight and maternal glucose tolerance during normal gestation.

Parameters of brain development were studied in near term guinea-pigs in relation to fetal weight and maternal glucose tolerance during normal gestation. Seven litters (22 fetuses) were studied. Fetal weight ranged from 43 to 94 g (119% variability) and the maternal glucose index (sum of the 7 serum glucose levels during the oral glucose tolerance tests) from 921 to 1,528 mg/dl (66% variability). The weights of the cerebrum and cerebellum were less affected by changes of fetal weight compared to other fetal organs. Significant correlations were observed between the maternal glucose index and brain cell number (DNA) and myelination (cerebroside-sulfatide). These variables did not correlate with fetal weight. Liver weight (% fetal weight) and cell number also correlated with the maternal glucose index. It is speculated that the amount of glucose available to the brain could be responsible for the relative protection of the brain to fetal malnutrition and also for the link between maternal glucose index and parameters of fetal brain development.

Animals↗
PubMed1996

Membrane components separate early-onset Alzheimer's disease from senile dementia of the Alzheimer type.

Brain tissue from 12 subjects with pure Alzheimer's disease (AD) and 21 subjects with senile dementia of the Alzheimer type (SDAT) was investigated for membrane lipids and compared with that in age-matched controls. In brain tissue from the patients with AD, phospholipids were significantly decreased compared with that from SDAT patients and controls, cholesterol was reduced compared with that in controls, and gangliosides were significantly reduced in all gray-matter areas investigated compared with those in both SDAT subjects and controls. A reduction in gangliosides also occurred in the SDAT group, but it was smaller. In the white matter, the pattern of changes was the opposite. Phospholipids, cholesterol, cerebroside, and sulfatide were significantly reduced in the frontal-lobe white matter in the SDAT group compared with that in age-matched controls and AD patients. Gangliosides in the cerebrospinal fluid also separated AD from SDAT and controls. The findings indicate synapse degeneration as an important pathogenetic factor in AD. This disorder should be separated from SDAT, in which white-matter degeneration appears to be more prominent.

Aged↗
PubMed2001

Interaction of cholesterol with sphingomyelin in mixed membranes containing phosphatidylcholine, studied by spin-label ESR and IR spectroscopies. A possible stabilization of gel-phase sphingolipid domains by cholesterol.

The ESR spectra from different positional isomers of sphingomyelin and phosphatidylcholine spin-labeled in their acyl chain have been studied in sphingomyelin(cerebroside)-phosphatidylcholine mixed membranes that contain cholesterol. The aim was to investigate mechanisms by which cholesterol could stabilize possible domain formation in sphingolipid-glycerolipid membranes. The outer hyperfine splittings in the ESR spectra of sphingomyelin and phosphatidylcholine spin-labeled on the 5 C atom of the acyl chain were consistent with mixing of the components, but the perturbations on adding cholesterol were greater in the membranes containing sphingomyelin than in those containing phosphatidylcholine. Infrared spectra of the amide I band of egg sphingomyelin were shifted and broadened in the presence of cholesterol to a greater extent than the carbonyl band of phosphatidylcholine, which was affected very little by cholesterol. Two-component ESR spectra were observed from lipids spin-labeled on the 14 C atom of the acyl chain in cholesterol-containing membranes composed of sphingolipids, with or without glycerolipids (sphingomyelin/cerebroside and sphingomyelin/cerebroside/phosphatidylcholine mixtures). These results indicate the existence of gel-phase domains in otherwise liquid-ordered membranes that contain cholesterol. In the gel phase of egg sphingomyelin, the outer hyperfine splittings of sphingomyelin spin-labeled on the 14-C atom of the acyl chain are smaller than those for the corresponding spin-labeled phosphatidylcholine. In the presence of cholesterol, this situation is reversed; the outer splitting of 14-C spin-labeled sphingomyelin is then greater than that of 14-C spin-labeled phosphatidylcholine. This result provides some support for the suggestion that transbilayer interdigitation induced by cholesterol stabilizes the coexistence of gel-phase and "liquid-ordered" domains in membranes containing sphingolipids.

Brain Chemistry↗
PubMed1980

Calorimetric investigation of the complex phase behavior of glucocerebroside dispersions.

The thermotropic behavior of aqueous dispersions of glucocerebroside from Gaucher's spleen has been investigated by different scanning calorimetry. These results indicate that glucocerebroside undergoes two distinct phase transitions centered at 47 and 83 degrees C, respectively. The high-temperature transition is associated with the main gel-liquid crystalline transition and has an enthalpy change of 13.6 kcal/mol of lipid; this transition is not rapidly reversible and the liquid crystalline phase supercools to a metastable gel phase. The low-temperature transition is exothermic with an enthalpy change of -6.3 kcal/mol and involves a transformation of the metastable gel phase to a more highly ordered gel conformation, without involving changes in the conformational state of the hydrocarbon chains. The behavior of these transitions as a function of the amount of water suggests that the origin of the metastability is related to a hydration-dehydration process of the cerebroside molecule. Experiments with synthetic-D-erythro-N-palmitoylglucocerebroside revealed the same thermotropic behavior. These glucocerebroside transitions are irreversible and together define a unidirectional cycle in which each state of the molecule can only be reached by completing the entire cycle.

Calorimetry, Differential Scanning↗
PubMed2002

Self-organizing properties of natural and related synthetic glycolipids.

In this article we report on the syntheses, self-organizing properties, and structures of a variety of cerebrosides and related synthetic glycolipids. The thermotropic and lyotropic liquid crystalline properties of the materials were evaluated in detail. All of the families of materials studied exhibited columnar mesophases. In the dry state the aliphatic chains were found to be located on the exterior of the columns, whereas in the wet state the reverse was the case with the polar headgroups on the exterior. Thus, the aliphatic chains act almost like hydrocarbon solvents in the dry state.

Cerebrosides↗
PubMed2001

Novel ceramides from the fungus Lactarium volemus.

Two novel ceramides, lactariamides A (N-2'-hydroxytetracosanoyl-2-amino-3,4-epoxyoctadecan-1-ol (1)) and B ((4E,8E)-N-2'-hydroxyoctadecanoyl-2-amino-9-methyl-4,8-octadecadine-1,3-diol (2)), were isolated from the fungus Lactarium volemus, together with a known compound, cerebroside D (3). Their structures were determined on the basis of chemical evidence and spectral methods.

Agaricales↗
PubMed2003

New glycosphingolipids from the fungus Catathelasma ventricosa.

Three new glycosphingolipids with a cis-Delta(17)-fatty acyl moiety, namely, catacerebrosides A-C (1-3), along with two known glycosphingolipids, cerebrosides B and D, six known ergostane-type sterols, and tyrosamine were isolated from the fungus Catathelasma ventricosa. The structures of 1-3 were elucidated on the basis of spectroscopic analysis and chemical methods.

Cerebrosides↗
PubMed2005

Antineoplastic agents. 545. Isolation and structure of turbostatins 1-4 from the Asian marine mollusk Turbo stenogyrus.

The cancer cell line bioassay-guided separation of an extract from the marine mollusk Turbo stenogyrus led to the isolation of four new cerebrosides designated turbostatins 1-4 (1-4). The structure of each glycolipid was determined by interpreting results of a series of HR-APCI-MS and NMR (1D and 2D) spectral analyses. All four turbostatins exhibited significant (GI50 0.15-2.6 microg/mL) cancer cell growth inhibition against the murine P388 lymphocytic leukemia and a panel of human cancer cell lines.

Animals↗
PubMed2004

Activity-guided fractionation of the leaves of Ormosia sumatrana using a proteasome inhibition assay.

Activity-guided fractionation of a chloroform-soluble extract of the leaves of Ormosia sumatrana, using a proteasome inhibition assay, led to the isolation of a new A-type proanthocyanidin derivative, 3'-O-cinnamoylprocyanidin A-2 (1), and a new cerebroside, sumatranoside (2). The structures of these two isolates were determined as epicatechin-(2 beta-->O-->7',4 beta-->8')-epicatechin-3'-O-cinnamate (1) and 1-O-(beta-d-glucopyranosyl)-(2S,3S,4R)-2N-[(2'R)-2'-hydroxy-tetracosanoyl]-9Z-octadecene-1,3,4-triol (2), respectively, by spectroscopic and chemical methods. Sumatranoside (2) exhibited proteasome inhibitory activity with an IC(50) value of 30 microM.

Catechin↗
PubMed1998

Metachromatic leukodystrophy: molecular genetics and an animal model.

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulphatase A (ASA; EC 3.1.6.8). Deficiency of this enzyme causes intralysosomal storage of the sphingolipid cerebroside sulphate. This lipid is abundant in myelin and it may thus not be surprising that storage mainly affects oligodendrocytes. Patients suffer from a progressive demyelination causing various neurological symptoms. The disease is fatal and treatment is not available. The human ASA gene has been cloned and more than 40 mutations have been analysed that cause metachromatic leukodystrophy. Few of these alleles are frequent among patients, whereas most mutant alleles have only been found in single families. Since MLD has only been described in humans and no naturally occurring animal model has been described, ASA-deficient mice have been generated by homologous recombination. The ASA knockout mice are unable to degrade sulphatide and store the lipid intralysosomally. The pattern of lipid storage in neuronal and non-neuronal tissues resembles that described for patients. In the nervous system, lipid storage is found in oligodendrocytes, astrocytes and some neurons. Animals display an astrogliosis and a decreased average axonal diameter. Purkinje cells and Bergmann glia of the cerebellum are morphologically aberrant. Demyelination is seen in the acoustic ganglion and occurs between the ages of 6 and 12 months. The animals are deaf at this age and display various neuromotor abnormalities. However, compared to humans the mice have a surprisingly mild phenotype, since they have a normal life span and do not develop widespread demyelination. ASA-deficient mice have been transplanted with bone marrow, which was transduced with a retroviral vector expressing arylsulphatase A. The majority of transplanted animals display sustained expression of arylsulphatase A from the retroviral construct up to 5 months after transplantation. However, preliminary data suggest that this therapeutic approach does not reduce storage material.

Animals↗
PubMed1997

Molecular interactions of the major myelin glycosphingolipids and myelin basic protein in model membranes.

The molecular organization, interactions, phase state and membrane-membrane interactions of model membranes containing cerebroside (GalCer), sulfatide (Sulf) and myelin basic protein (MBP) were investigated. Sulf shows a larger cross-sectional area than GalCer, in keeping with the lateral electrostatic repulsions in the negatively charged polar head group. The interactions of GalCer with different phospholipids are similar while those with Sulf depend on the phosphoryl choline moiety in the phospholipid. MBP induces a decrease of the phase transition temperature in both lipids but with Sulf this occurs at lower proportions of MBP. In mixtures of Sulf with phosphatidylcholine MBP induces phase separation among Sulf-rich and PC-rich domains. Extensive apposition of bilayers containing Sulf is induced by MBP while GalCer interferes with this process. Few membrane interactions proceed to bilayer merging or whole bilayer fusion and the glycosphingolipids help preserve the membrane integrity.

Animals↗
PubMed1970

The identity of a myelin-like fraction isolated from developing brain.

1. A myelin-like membrane fraction was isolated from developing rat brain by a new method. 2. The chemical composition and morphology of the fraction are described. 3. The myelin-like fraction is similar to myelin in characteristic enzyme activity but differs in the absence of basic protein and cerebrosides. No similarity to other subcellular fractions was observed. 4. It is suggested that the myelin-like fraction is a stage in the formation of compact myelin from glial plasma membrane. 5. ;Early' myelin consists of the myelin-like and compact myelin fractions from developing brain.

Animals↗
PubMed1971

Occurrence of long-chain fatty acids and glycolipids in the cell envelope fractions of baker's yeast.

1. The total yield of fatty acids from the whole envelopes was markedly higher than that obtained from the ordinary cell walls. In both samples the major fatty acids were C(16) and C(18) acids. 2. The whole envelopes contained C(18) acids and long-chain (C(19)-C(26)) fatty acids, in a higher proportion than did the ordinary cell walls. Fifteen fatty acids with more than 18 carbon atoms were identified, among which 2-hydroxy-C(26:0) and C(26:0) acids predominated. 3. A complex sphingolipid containing inositol, phosphorus and mannose was isolated from the whole cell envelopes. The main fatty acids of this lipid were 2-hydroxy-C(26:0) and C(26:0) acids. It was concluded that this sphingolipid is present both in the ordinary cell wall and in the plasma membrane of baker's yeast. 4. The neutral lipids amounted to over 50% and the glycerophosphatides to about 30% of the total fatty acid content of the whole envelope. The major fatty acids in these lipids were C(16:1), C(18:1) and C(16:0) acids. The proportion of fatty acids with more than 18 carbon atoms was lowest in the neutral lipids, whereas the neutral glycolipids contained the highest percentage of these fatty acids. Acidic glycolipids amounted to 14% of the total fatty acid content of the whole envelope. The presence of a cerebroside sulphate in this lipid fraction was demonstrated, whereas the high content of 2-hydroxy-C(26:0) acid found is caused by the complex inositol- and mannose-containing sphingolipid.

Cell Fractionation↗