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PubMed1984

Effect of 3-acetylpyridine on the content of myelin in the developing rat brain.

Suckling rats were given 3-acetylpyridine, an antagonistic agent of nicotinic acid, on the 6th day after birth. The quantity of myelin and cerebroside, total lipid synthesis, and activities of fatty acid synthetase and fatty acyl-CoA elongating enzyme were measured in rats which received 3-acetylpyridine. At both 20 days and 30 days of age, rats which had received 3-acetylpyridine showed lower values in body weight, myelin yield, cerebroside level and specific activity of brain 2',3'-cyclic nucleotide-3-phosphohydrolase, when compared with those of the controls. Biosynthetic activity of lipid in brain slices of rats which had received 3-acetylpyridine was about 50% less than that of the controls. Moreover, activities of the microsomal palmitoyl-CoA, stearoyl-CoA and arachidyl-CoA elongating systems in the brain of rats which had received 3-acetylpyridine were about 80%, 50% and 50% those of the controls, respectively. These findings imply that 3-acetylpyridine affects the synthesis of long chain fatty acid in the developing rat brain. Therefore, nicotinic acid may play an important role in myelination associated with the synthesis of cerebrosides which contain high levels of long chain fatty acids.

Animals↗

PubMedDate not supplied

[Brain glycolipids in experimental brain edema].

Quantitative and qualitative composition of gangliosides, sulfatides and cerebrosides were studied in normal state and in experimental brain edema by means of thin-layer chromatography. In the experimental edema content of mono- and disialogangliosides was decreased while tri- and tetrasialogangliosides were unaltered. Statistically distinct increase in content of sulfocerebrosides (sulfatide 1.2) was also detected in brain edema as compared with controls. At the same time, amount of cerebroside 2 was decreased, whereas increase in cerebroside I concentration was detected.

Animals↗

PubMed1987

[Lipid composition of human malignant brain tumors].

Malignant transformation is characterized by the uncontrolled proliferation of cells. And changes in the composition of glycolipids, cell surface component which may be involved in regulation of cell growth, were often observed in the malignant transformation. In this study, cholesterol, lipid-bound phosphorus, cerebroside, sulfatide and ganglioside were quantitated in the tissue of 20 human malignant brain tumors (malignant glioma, 8; low grade glioma, 4; metastatic tumor, 7; malignant meningioma, 1). As compared with normal brain, all tumor tissue contained lower cholesterol, sialic acid, cerebroside and sulfatide. Metastatic brain tumor or glioma showed characteristic patterns in the content of ganglioside, cerebroside and sulfatide respectively. The ganglioside patterns of metastatic tumor or glioma contained a greater proportion of structurally simpler gangliosides than normal brain. And in metastatic tumor, GM3 was a major ganglioside. On the contrary, glioma had increased proportion of GM3 and GD3 gangliosides. High grade glioma such as Grade 3-4 contained higher proportion of GM3 and GD3, whereas low grade glioma (Grade 1-2) contained less proportion of GM3 and GD3.

Brain Neoplasms↗

PubMed1968

6-acyl galactosyl ceramides of pig brain: structure and fatty acid composition.

Two glycolipids were isolated from pig brain and were shown to be the fatty acid esters of kerasin and cerebron in which the second fatty acid moiety is attached to the 6-position of the galactose. The point of attachment was shown in two ways: by permethylation and by cleavage with periodate. Methanolysis of the permethylated cerebroside esters yielded O-methyl sphingosines, methyl esters of nonhydroxy or 2-methoxy acids, and methyl 2,3,4-trimethyl galactoside. Cleavage of the cerebron ester with periodate, followed by treatment with sodium borohydride and dilute HCl, yielded ceramide plus 1-monoglyceride. The ester-linked fatty acids were primarily 16:0, 18:0, and 18:1, while the amide-linked fatty acids showed the wide assortment of chain lengths typical of brain cerebrosides. The methylation step, with silver oxide and methyl iodide, yielded two derivatives with the cerebroside esters, but the structural explanation for the difference was not elucidated. The galactose in the cerebron ester was shown to exist in the beta-pyranoside form.

Animals↗

PubMedDate not supplied

[Brain lipids of a mammoth, Elephas primigenius, which died more than 40,000 years ago].

Studies have been made on the brain lipids of the 6--7-month mammoth which remained in the eternal ice for more than 40.000 years. Thin layer chromatography of chloroformmethanol extract of the brain lipids shows that all glycerophospholipids in the brain were destroyed. On the contrary, sphingophospholipid sphingomyelin yielded the evident spot which was identified by specific reactions and by comparison with sphingomyelin from the brain of rat. Sphingomyelin content was evaluated. Using gas-liquid chromatography, fatty acid composition of sphingomyelin was investigated. It was found to be close to that in contemporary mammals. Other shingolipids -- cerebrosides, sulfatides, gangliosides -- persisted (probably, only partially) and were studied quantitatively. Relative content of cerebrosides with normal fatty acids and hydrooxyacids was determined. Studies were also made on fatty acid composition of cerebrosides, sulfatides and gangliosides, as well as on the composition of spingosine bases of gangliosides. Free cholesterol was found in the brain of the mammoth. Other sterols were not detected. With respect to quantitative evaluation of the preserved lipids, it should be mentioned that on the one hand, the brain underwent dehydration which increased lipid content per a unit of "wet" weight, whereas on the other one lipids were partially degraded, this process decreasing their content.

Animals↗

PubMed1970

Fatty acids of glycosphingolipids from pig blood fractions.

Four glycolipids have been isolated from three fractions of pig blood. The glycolipids were presumably cerebroside, diglycosyl ceramide, triglycosyl ceramide, and globoside. The blood fractions were erythrocytes and plasma high and low density lipoproteins. Fatty acid distributions were determined for each glycolipid as a means to assist in identifying relationships among the several glycolipids. Normal fatty acids predominated in all glycolipids except the globosides from erythrocytes in which the amount of hydroxy acids was slightly greater than the amount of normal acids. Hydroxy acids appeared to be present in all the glycolipids, but the concentration was very low in cerebrosides isolated from high density lipoproteins and erythrocytes, and in diglycosyl ceramide and globoside of the low density lipoproteins. In general, the average fatty acid chain length increased from cerebroside to globoside. This was most apparent in erythrocytes and also greater for normal acids than for hydroxy acids. Fatty acid distributions of erythrocyte glycolipids had sufficient variation to make a metabolic relationship by simple addition of a hexose appear doubtful. While the fatty acid distributions found in plasma lipoproteins were more similar, some means of acyl group selection is probably present for either the synthesis or degradation of these glycolipids.

Animals↗

PubMed1966

Changes in sphingosine and fatty acid components of the gangliosides in developing rat and human brain.

Rat brain increases in weight after birth in three stages: (I) rapidly for the first 2 weeks, (II) at a lower rate from 2 to 5 weeks, and (III) at a still lower rate from 5 weeks to 5 months. During the succeeding period, designated IV, it maintains constant weight up to 1 year of age. Brain ganglioside content increased linearly during I and II, more slowly during III, and diminished during IV. The appearance of measurable amounts of brain sphingomyelin and cerebroside succeeded that of ganglioside. Ceramide with C18-sphingosine and C18 fatty acid was found in a large proportion of all three sphingolipids upon their first appearance in measurable quantity. C18 fatty acid in cerebroside rapidly declined to a negligible level, while in gangliosides and sphingomyelin it declined slowly but remained the major fatty acid component. Cerebrosides and sphingomyelin contained C18-sphingosine almost exclusively at all stages of rat brain growth. Gangliosides contained C18-sphingosine almost exclusively at birth, but subsequently accumulated C20-sphingosine until they had nearly equal quantities of each base type. Changes in human brain gangliosides resemble those in rat. In Tay-Sachs disease, gangliosides have C18-sphingosine predominantly, and a high content of C18 fatty acid.

Adult↗

PubMedDate not supplied

[Effect of glycosphingolipids on erythrocyte Na+,K+-ATPase activity].

The total fractions of gangliosides and cerebrosides isolated from the tissue of human brain were studied for their effect on the Na+, K+-ATPase activity of native erythrocytes and their membranes. It is shown that gangliosides depending on time of their preincubation with the enzyme preparation and concentration produce both the activating and inhibiting action and cerebrosides--only the inhibiting one. Gangliosides inhibit the transport ATPase activity noncompetitively with respect to ATP and Na+ and competitively--to K+, cerebrosides inhibit it noncompetitively with respect to all ATPase activators.

Cerebrosides↗

PubMedDate not supplied

[Incorporation of 2-14C-acetate into the glycolipids of the spinal cord and brain stem of normal guinea pigs and guinea pigs in the paralytic stage of triorthocresylphosphate poisoning].

Paralytical form of chronic intoxication was caused by single intracutaneous administration of tri-O-cresyl phosphate (TOCP)/2=2.2 ml/kg/ into guinea pigs. Within the first 27--33 days after the treatment, the animals with pronounced symptoms of neurotoxic effect of TOCP were subcutaneously administered with 2-14C-acetate/100 mu Ci per 100 g of body weight/2 hrs before decapitation. Purified cerebrosides, gangliosides and acid-soluble fraction, containing 14C-precursors, were isolated and their specific radiactivity was measured in a gas-flow counter. The rate of 14C incorporation into cerebrosides and gangliosides in spinal cord was found to exceed that in brain stem. In paralytical stage of disease, caused by TOCP, synthesis of cerebroside was depressed in spinal cord and in brain stem, according to calculated value for relative specific radioactivity. In spinal cord the rate of 14C incorporation into gangliosides was also decreased. These data suggest that neurtoxic drug TOCP affects metabolic processes both in oligodendroglial cells and in neurons, where ganglioside biosynthesis occurs.

Acetates↗

PubMedDate not supplied

[Age characteristics of glycolipid distribution in rat tissues depending on the functional state of the thyroid gland].

Distribution of the content of cerebrosides in the rat tissues is established to be nonuniform for the series brain greater than spleen greater than lungs greater than liver greater than kidneys greater than heart greater than muscles. In the new born animals only traces of cerebrosides and considerable amounts of gangliosides are found. In the process of the morphological and functional maturing all the tissues get enriched by cerebrosides (till 45 days) and gangliosides (by 15 days) with their content decrease in certain tissues in the process of ageing. Experimental hypothyrosis is accompanied by a fall of the total content and a decrease in the amount of hormonal iodine in the tissues, the decrease being more significant in young animals. The age dynamics of the glycolipid content inthe tissues is maintained, but their highest accumulation is delayed and does not reach the maximum characteristics of the intact animals.

Animals↗

PubMed1980

Glucosylceramide uptake protein from spleen cytosol.

Incubation of rat red cells with liposomes containing radioactive glucosylceramide, together with unlabeled phosphatidylcholine and cholesterol, produced cells labeled with the glycolipid. Part of the bound cerebroside could be removed by further incubation with unlabeled liposomes. Both processes, uptake and release, were stimulated by adding a preparation obtained from bovine spleen. The active material was purified partially by ammonium sulfate precipitation and gel permeation with a Sephadex G-75 column. The latter step indicated a molecular weight of about 22,000. The material lost much of its activity when treated with trypsin or N-ethylmaleimide, indicating that it is a protein. The "cerebroside uptake protein" was quite stable if stored in dithioerythritol at 4 degrees C. Tests with liposomes containing labeled phosphatidylcholine or cholesterol showed that the red cells took up these lipids as well, but the transfer protein exerted little effect on this. Ghosts prepared from rat red cells also took up the three lipids from the liposomes and here, as well, the uptake protein showed high specificity in facilitating the uptake of cerebroside. This appears to be the first demonstration of the existence of a glycolipid transfer protein. Possible physiological roles for the uptake protein in red cell metabolism and in the modulation of the glycosphingolipid composition of cell membranes are discussed.

Animals↗

PubMed1995

[Sphingolipid changes in rat cerebral cortex during focal ischemia--how does ceramide accumulate in an ischemic condition?].

Levels of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia produced by middle cerebral artery occlusion. Ceramide began to increase at 6 hours of ischemia and increased to 4.5 folds at 96 hours. Amino-linked fatty acids in increased ceramide were composed solely of non-hydroxy fatty acids, and stearic acid was the most prominent. Sphingomyelin, whose amino-linked fatty acids were mostly stearic acid, decreased in a time-dependent manner and became about a half of controls at 96 hours. Hydroxy fatty acid linked cerebroside decreased at and after 6 hours of ischemia, whereas significant decrease of non-hydroxy fatty acid linked cerebroside occurred only at 96 hours of ischemia. There were no measurable changes in the levels of gangliosides. The results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during ischemia.

Animals↗

PubMed2004

Sulfatide is a negative regulator of oligodendrocyte differentiation: development in sulfatide-null mice.

Galactosylceramide (GalC) and its sulfated analogue, sulfatide, are major galactosphingolipid components of myelin and oligodendrocyte plasma membranes in the nervous system. We previously hypothesized that these galactolipids play functional roles in the regulation of oligodendrocyte terminal differentiation by acting as sensors/transmitters of environmental information. Evidence strongly supports this idea. First, these molecules are initially expressed on the cell surface at the interface at which oligodendrocyte progenitors first enter terminal differentiation. Second, exposure of oligodendrocyte progenitors to anti-GalC/-sulfatide (RmAb) or antisulfatide (O4), but not anti-GalC (O1), antibodies leads to the reversible arrest of oligodendrocyte lineage progression at this interface. Third, in cerebroside galactosyl transferase-null mice (Cgt(-/-)) that are unable to synthesize either GalC or sulfatide, terminal differentiation and morphological maturation of oligodendrocytes are enhanced. In the present study, we examined oligodendrocytes differentiation in cerebroside sulfotransferase-null mice (Cst(-/-)) that lack sulfatide but express GalC. We show that cerebroside sulfotransferase mRNA expression begins already in the embryonic spinal cord and progressively increases with age, that the late progenitor marker POA is not synthesized in the absence of this enzyme, and that, most notably, there is a two- to threefold enhancement in the number of terminally differentiated oligodendrocytes both in culture and in vivo, similar to that in mice lacking both GalC and sulfatide. We conclude that primarily sulfatide, rather than GalC, is a key molecule for the negative regulation of oligodendrocyte terminal differentiation.

Animals↗

PubMed1996

A microwave-mediated saponification of galactosylceramide and galactosylceramide I3-sulfate and identification of their lyso-compounds by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

Small amounts of galactosylceramide (cerebroside) and galactosylceramide I3-sulfate (sulfatide) obtained from porcine spinal cord and equine kidney were deacylated by a rapid method of microwave-mediated saponification to prepare their lyso-compounds. Mass spectra of their protonated or deprotonated molecular ion peaks were detected by recently developed new technology of a delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometer with reflector detector in positive or negative ion mode. Long chain bases of lysocerebroside and lysosulfatide were different between porcine spinal cord and equine kidney, but similar to each other in the same organ, suggesting their common synthetic pathway. It is noted that the new rapid method can be similarly applied to the deacylation of both cerebroside and sulfatide in contrast to our classical method which was able to be applied to cerebroside, but not to sulfatide.

Animals↗

PubMed1981

Triethyllead treatment of cultured brain cells. Effect on accumulation of radioactive precursors in galactolipids.

Cultured cells from chick embryo brains were studied for their sensitivity to triethyllead. Triethyllead chloride (3.16 microM) was added to the nutrient medium and incubated for 48 hr with the cells. Morphological changes in light microscope and radioactive labeling of galactolipids were assayed. Triethyllead treatment reduced the number of neuronal cells with processes. Morphological changes were not observed in glial cells. The [35S]sulfate labeling of sulfatides was reduced to 50%. The [3H]serine labeling of cerebrosides with alpha-hydroxy fatty acids was not influenced, while the [3H]serine labeling of cerebrosides with nonhydroxy fatty acids was inhibited 40% in one- and two- but not in three-week-old cultures. The results indicate that the nerve cell response to triethyllead in cultures is selective, since the neurons are more sensitive than the glia cells and the labeling of sulfatides is more sensitive than that of cerebrosides.

Animals↗

PubMed1982

Effects of cell density on the neutral glycolipid composition of cultured human brain and glioma cells.

Density dependent chain elongation of neutral glycosphingolipids (NGSL) is associated with contact inhibition of mitosis in several normal cultured cell lines. Transformed non-neural cell lines which have impaired contact inhibition frequently lose this biochemical response. To determine if either of these phenomena occur in human neural cells we determined NGSL compositions of cultured glioblastoma multiforme and normal fetal brain cells. Fetal cells generally had more total NGSL than the tumor cells. As a percentage of total NGSL, both cell lines at higher cell densities had larger proportions of ceramide trihexoside and globoside, but smaller proportions of cerebroside. This decrease was mainly in non-hydroxy fatty acid cerebroside of glioma cells, but in hydroxy fatty acid cerebroside of normal fetal brain cells. These results demonstrate that although glioblastoma multiforme cells have markedly impaired growth control, they still preserve density dependent chain elongation of NGSL. A role for this phenomenon in normal cellular growth control has yet to be established.

Aged↗

PubMed1979

Short chain ceramides as substrates for glucocerebroside synthetase. Differences between liver and brain enzymes.

In order to increase the sensitivity of the assay for ceramide: UDPGlc glucosyltransferase, the enzyme that makes glucocerebroside, we synthesized a variety of ceramide homologues that might be better substrates than the naturally occurring ceramides. N-Octanoyl sphingosine proved to be the best lipid tested in liver and brain. It could be added to the tissue homogenate in the dry form, as a thin layer coated on Celite, or in liposomes, prepared from lecithin and cerebroside sulfate. The liposomal form produced better replication of assay values. It is suggested that the addition of cerebroside sulfate to liposomal preparations might be a good, and more physiological, replacement for the commonly used dicetyl phosphate. A new homologue of DL-sphinganine, decasphinganine, was synthesized by an efficient series of steps and acylated with different fatty acids to form ceramide homologues. The best substrate in this series was the lauroyl amide and it is suggested that this lipid be used in cerebroside synthetase assays because of the convenience of preparing it, even though it is not as good as octanoyl sphingosine. Both compounds are distinctly better than natural ceramide or DL-sphinganine amides. From comparisons of enzyme activity under various conditions, the tentative conclusion is drawn that the enzymes in liver and brain have different properties, and that liver has two different synthetases.

Amides↗

PubMed1985

Inhibition of rat brain galactocerebroside sulfotransferase by triazine aromatic dyes: interaction with the 3'-phosphoadenosine 5'-phosphosulfate binding site.

The mechanism of inhibition of rat brain cerebroside sulfotransferase (EC 2.8.2.11) by a series of triazine aromatic dyes was examined. These dyes are putative site-specific probes of the "dinucleotide fold". All of the dyes examined were competitive inhibitors of cerebroside sulfotransferase with respect to 3'-phosphoadenosine 5'-phosphosulfate (PAPS) binding. In addition, the binding of the dye, Congo Red, to the sulfotransferase was associated with a red shift in its absorption spectrum. Based on these results, it is suggested that rat brain cerebroside sulfotransferase contains a "dinucleotide fold" as a structural feature of the protein.

Adenine Nucleotides↗