Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CEREBROSIDES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources
PubMedDate not supplied

Changes in the lipids of human articular cartilage with age.

Histochemical and chemical studies demonstrated a significant increase in the lipods of articular cartilage with advancing age. Triglycerides, cholesterol, and phospholipids were identified chemically and were shown by comparative staining procedures to be present in intracellular and extracellular lipids. The distribution and the composition of the extracellular lipids were interpreted as indicating that the extracellular lipids are of cellular origin. Glycolipids were extracted from cartilage of all ages and were shown to account for a portion of the increase in total lipid with age. Glycolipids extracted from aged cartilage were partially characterized. Cerebrosides, sulfatides, and gangliosides were detected. Glycolipids were estimated to comprise from 5 to 10% of the total lipid of articular cartilage. Arachidonic acid concentrations increased maredly with age in the surface of cartilage but were present in trace amounts in deep cartilage, demonstrating clear-cut differences in the levels as well as the location of this fatty acid precursor of the prostaglandins (PGE2 and PGF2alpha).

Adolescent↗
PubMed1989

Desorption of ions from rat membranes: selectivity of different ionization techniques.

Complex lipid biomarkers, including phosphatidylcholines, cerebrosides and sulfatides, are shown to be desorbed intact from rat brain myelin and rat liver microsomes by liquid secondary ion mass spectrometry, by plasma desorption and by laser desorption. Different polar lipids are favored by the different desorption techniques and as negative or positive ions. These selectivities support current theories about ionization for the different techniques.

Animals↗
PubMed2004

Lactosylsulfatide expression in hepatocellular carcinoma cells enhances cell adhesion to vitronectin and intrahepatic metastasis in nude mice.

Lactosylsulfatide (SM3), one of the major sulfated glycolipids, has been reported to be involved in cellular adhesion. Yet, its specific function has not been well understood in tumor biology, especially in the process of metastasis. We analyzed expression levels of sulfatide on HCC cells with different metastatic potentials and found that levels were correlated with metastatic potential. Next, the cerebroside sulfotransferase (CST) (EC2.8.2.11) gene, which synthesizes SM3 as well as galactosylsulfatide (SM4), was transfected into the HCC line Hep3B. Cell surface expression of SM3 was confirmed by thin-layer chromatogram immunostaining and flow-cytometric analyses. SM3-expressing Hep3B cells showed elevated expression of integrin alphaVbeta3 and higher adhesive ability to vitronectin compared to mock cells. Furthermore, SM3 expression promoted intrahepatic metastasis in nude mice. Thus, SM3 may play an important role in the metastasis of HCC cells by causing the interaction of integrin alphaVbeta3 with vitronectin.

Animals↗
PubMed1993

Thrombospondin related anonymous protein (TRAP) of Plasmodium falciparum binds specifically to sulfated glycoconjugates and to HepG2 hepatoma cells suggesting a role for this molecule in sporozoite invasion of hepatocytes.

Thrombospondin related anonymous protein (TRAP) of Plasmodium falciparum contains an amino acid motif based around the sequence WSPCSVTCG which is also found in region II of the circumsporozoite (CS) proteins of different species of Plasmodium. This amino acid motif confers on the CS protein the ability to bind specifically to sulfated glycoconjugates and to hepatocytes. This suggests that the interaction of CS protein with sulfated glycoconjugates on the surface of the hepatocytes may represent the first molecular event of sporozoite invasion of liver cells. Experimental evidence indicates that TRAP is localized both on the micronemes and on the surface of P. falciparum sporozoites implying that TRAP with its putative sulfated glycoconjugate binding motif may also be involved in recognition and/or entry of hepatocytes by the sporozoite. We show here that different TRAP constructs expressed in Escherichia coli bind to sulfogalactosyl-cerebrosides (sulfatides) and to the surface of HepG2 cells. These interactions are dependent on the presence of the conserved amino acid motif WSPCSVTCG within the sequences of the constructs and are completely inhibited by several sulfated glycoconjugates as well as by suramin, a polysulfonated drug with anti-protozoan activity. Moreover, sporozoite invasion of HepG2 cells is inhibited by antisera raised against these different TRAP constructs and by the presence of low concentrations of suramin. We concluded that TRAP may be one of the parasite encoded molecules in the host-parasite interaction that results in sporozoite invasion of hepatocytes.

Amino Acid Sequence↗
PubMed2003

The phosphorylation state of neuronal processes determines growth cone formation after neuronal injury.

Growth cones are essential for neuronal pathfinding during embryonic development and again after injury, when they aid in neuronal regeneration. This study was aimed at investigating the role of kinases in the earliest events in neuronal regeneration, namely, the formation of new growth cones from injured neuronal processes. Neurites of identified snail neurons grown in vitro were severed, and the formation of growth cones was observed from the ends of such transected processes. Under control conditions, all neurites formed a new growth cone within 45 min of transection. In contrast, growth cone formation in the presence of a general kinase inhibitor, K252a, was significantly inhibited. Moreover, decreasing the phosphorylation state of neurites by activating protein phosphatases with C2-ceramide also reduced growth cone formation. Pharmacological analysis with specific kinase inhibitors suggested that targets of protein kinase C (PKC) and tyrosine kinase (PTK) phosphorylation control growth cone formation. Inhibition of PKC with calphostin C and cerebroside completely blocked growth cone formation, whereas the inhibition of PTK with erbstatin analog significantly reduced growth cone formation. In contrast, inhibitors of protein kinase A, protein kinase G, CaM-kinase II, myosin light-chain kinase, Rho kinase, and PI-3 kinase had little or no effect 45 min after transection. These results suggest that the transformation underlying the formation of a growth cone from an injured (transected) neurite stump is highly sensitive to the phosphorylation state of key target proteins. Therefore, injury-induced signaling events will determine the outcome of neuronal regeneration through their action on kinase and phosphatase activities.

Animals↗
PubMed2004

Co-clustering of galactosylceramide and membrane proteins in oligodendrocyte membranes on interaction with polyvalent carbohydrate and prevention by an intact cytoskeleton.

We have shown previously that addition of liposomes containing the two major glycosphingolipids of myelin, galactosylceramide (GalC) and cerebroside sulfate (CBS), to cultured oligodendrocytes (OLs) caused clustering of GalC on the extracellular surface and myelin basic protein (MBP) on the cytosolic surface to the same membrane domains. It also caused depolymerization of actin microfilaments and microtubules, indicating that interaction of the liposomes with the OL surface induces transmembrane signal transmission. We show that a multivalent form of galactose conjugated to bovine serum albumin has a similar effect as the multivalent GalC/CBS-containing liposomes. Because GalC and CBS can interact with each other across apposed membranes and because anti-GalC and anti-CBS antibodies also cause redistribution of GalC/CBS and depolymerization of microtubules, we believe that the multivalent carbohydrate interacts with GalC and CBS in the OL membrane. Several myelin-specific transmembrane proteins could be involved in this transmembrane signal transmission from GalC/CBS. We looked at co-clustering of several myelin constituents by confocal microscopy to determine if they are located in or redistribute to GalC/MBP-containing domains. Myelin oligodendrocyte glycoprotein (MOG), proteolipid protein (PLP), MAPK, and some phosphotyrosine-containing proteins were found to co-cluster with GalC and MBP, but myelin-associated glycoprotein (MAG) and phosphatidylinositol-4,5-bisphosphate (PIP(2)) did not. These results suggest that MOG and PLP, but probably not MAG, are possible candidates for transmembrane transmission of the signal received by GalC/CBS. To determine if depolymerization of actin microfilaments was required for co-clustering, or was secondary to clustering, we stabilized F-actin with jasplakinolide. This also prevented depolymerization of the microtubules and prevented clustering of all constituents, including GalC. The prevention of clustering or redistribution of these glycolipids and proteins by an intact cytoskeleton is consistent with the picket fence model.

Actins↗
PubMed2006

Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice.

Caloric restriction (CR), which improves health and increases longevity, was studied as a therapy in a hexosaminidase beta knockout mouse model of Sandhoff disease (SD), an incurable neurodegenerative disease involving accumulation of brain ganglioside GM2 and asialo-GM2 (GA2). Adult mice were fed a rodent chow diet either ad libitum (AL) or restricted to reduce body weight by 15-18% (CR). Although GM2 and GA2 were elevated, no significant differences were seen between the Hexb-/- and the Hexb+/- mice for most brain phospholipids and cholesterol. Cerebrosides and sulfatides were reduced in the Hexb-/- mice. In addition, rotorod performance was significantly worse in the Hexb-/- mice than in the Hexb+/- mice. CR, which decreased circulating glucose and elevated ketone bodies, significantly improved rotorod performance and extended longevity in the Hexb-/- mice but had no significant effect on brain lipid composition or on cytoplasmic neuronal vacuoles. The expression of CD68 and F4/80 was significantly less in the CR-fed than in the AL-fed Hexb-/- mice. We suggest that the CR delays disease progression in SD and possibly in other ganglioside storage diseases through anti-inflammatory mechanisms.

3-Hydroxybutyric Acid↗
PubMed1975

Studies on neuronal lipid.

The procedure for bulk preparation of nerve-cell perikarya from pig brain-stem is briefly described. This method has definite merits with regard to the preservation of the intracellular structures as well as the preservation of the processes. The chemical composition of the isolated nerve-cell perikarya is presented. The nerve-cell perikarya are characterized by the absence of cerebroside and sulfatide. Diffuse distribution of ganglioside on the cell surface is suggested. The lipid content of the nerve-cell perikarya isolated by different methods is discussed. Lipid composition of the invertebrate nervous tissue is discussed. The submicrosomal membranes of rat brain are isolated, and their chemical and morphological properties are discussed. Ribosome-free membranes are characterized by the high content of glycolipids including gangliosides, as well as by the high activity of Na, K-ATPase, whereas ribosome-bound membranes are characterized by the absence of glycolipids, as well as by the low activity of Na, K-ATPase. The molecular organizations of lipid in submicrosomal membranes are demonstrated.

Adenosine Triphosphatases↗
PubMed1983

Investigations on myelination in vitro: IV. "Myelin-like" or premyelin structures in cultures of dissociated brain cells from 14--15-day-old embryonic mice.

The present study reports ultrastructural and biochemical data characteristic of myelin-related structures in 30- to 41-day-old cultures of dissociated brain cells from 14- to 15-day-old embryonic mice. Multilayered membranous material was identified and displayed an alternation of electron-lucent and electron-dense lamellae with a periodicity of 102 A. In these membranes, typical myelin constituents like basic protein, cerebrosides, sulfatides, and CNPase could be identified. Although we are still unable to distinguish if these membranes are premyelin or compact myelin, which could be partly degraded, these results indicate that cultured mouse brain cells retain, to a certain extent, potential to produce myelin-related membranes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1988

Maternal dietary restriction causes myelin and lipid deficits in the brain of offspring.

The relationship between brain myelination and nutritional insufficiency in suckling rats whose dams had a restricted dietary intake was studied. The undernourished pups were characterized by body weight and brain weight that were 40-70% and 82-88% that of controls throughout the suckling period. Myelin concentrations, whether expressed as mg protein or as mg myelin dry weight per g wet brain, were 30-40% of normally fed controls. Myelin of undernourished rats contained total lipid, cholesterol, phospholipids, and sphingolipids that were 42, 54, 39, and 48%, respectively of the control counterparts. There was no change in the mole ratio of cholesterol:phospholipids:sphingolipids (i.e., cerebroside + sulfatide) in myelin from undernourished rats. Concentrations of individual phospholipids and sphingolipids were lowered by approximately the same percentage. Despite long-lasting, irreversible stunting of whole-body and brain growth, concentrations of myelin and myelin lipids returned to control levels after nutritional rehabilitation. Since the observed effects are different from those of more commonly used models, the present form of undernutrition may offer a useful system for studying the relationship between myelin lipids and brain development.

Animal Nutritional Physiological Phenomena↗
PubMed1992

Specific binding of cytotactin to sulfated glycolipids.

The binding of the glial glycoprotein, cytotactin, to a variety of purified glycolipids was examined. Clear-cut evidence was found for binding of radiolabeled cytotactin to sulfatides purified from bovine brain, but the molecule did not bind to gangliosides or cerebrosides. The sulfatide binding was sensitive to pH and ionic strength and was dependent on the presence of divalent cations. Binding was inhibited by purified unlabeled cytotactin, by polyclonal antibodies to cytotactin, and by several monosaccharides and polysaccharides. It was not inhibited by fibronectin, a chondroitin sulfate proteoglycan, or the HNK-1 monoclonal antibody, all of which are known to bind to cytotactin. These findings raise the possibilities that sulfated glycolipids may function as cellular receptors for cytotactin and that binding by sulfatides may modulate the varied effects of cytotactin on cellular processes.

Animals↗
PubMed1985

Phase behavior of carbamyloxyphosphatidylcholine, a sphingolipid analogue.

The phase behavior of two series of phosphatidylcholines (PC) possessing carbamyloxy-linked fatty acids has been studied by differential scanning calorimetry. These non-natural phosphatidylcholines are of interest because they possess the capability of forming interlipid hydrogen bonds via the carbamyloxy function and as such can serve as a model for sphingolipids, the phase behavior of which is thought to be dominated by interlipid hydrogen bonding. Furthermore, carbamyloxyphosphatidylcholines form unusually stable liposomes, and thus have potential in drug delivery. Carbamyloxyphosphatidylcholines of the type di-(CnH2n+1NHCOO)-PC, where n = 13, 15, or 17, exhibit metastable polymorphism. Cooling from the liquid crystalline state results in formation of a metastable low-temperature polymorph I, which must transform into a stable low-temperature polymorph II before the liquid crystalline state can be reached again. Carbamyloxyphosphatidylcholines of the type 1-C16:0-2-(CnH2n+1NHCOO)-PC exhibit similar metastable polymorphism. This metastability is similar to that exhibited by certain cerebrosides and sphingomyelins and indicates that the sphingosine backbone is not a prerequisite for this type of metastability. Furthermore, the carbamyloxy group is reversed in orientation compared with the amide of sphingolipids (-NHCO- versus -CONH-), suggesting that the intermolecular hydrogen bonding potential, rather than some highly specific steric or conformational constraint, is responsible for the observed metastability of sphingolipids.

Calorimetry, Differential Scanning↗
PubMed1995

A human glial hybrid cell line differentially expressing genes subserving oligodendrocyte and astrocyte phenotype.

We have developed a series of immortal human-human hybrid cell lines that express phenotypic characteristics of primary oligodendrocytes, by fusing a 6-thioguanine-resistant mutant of the human rhabdomyosarcoma RD with adult human oligodendrocytes by a lectin-enhanced polyethylene glycol procedure. Hybrids were selected in an aminopterin-containing media. In contrast to the tumor parent cells, a hybrid clone M03.13 expressed surface immunoreactivity for galactosyl cerebroside and intracellular immunoreactivity for myelin basic protein (MBP), proteolipid protein (PLP), and glial fibrillary acidic protein (GFAP). Serum deprivation or chronic treatment with a protein kinase C activator 4-beta-phorbol 12-myristate 13-acetate (PMA), but not dibutyl cyclic adenosine monophosphate induced coordinate up-regulation or de novo induction of oligodendrocyte phenotypic markers with concomitant down-regulation of GFAP expression. Consistent with immunohistochemical studies, northern blot analysis demonstrated that both MBP and PLP mRNA were up-regulated in MO3.13 cells by PMA treatment. M03.13 cells provide an immortalized clonal model system suitable for study of gene expression subserving oligodendrocyte and astrocyte phenotypes.

Astrocytes↗
PubMed1987

Krabbe's disease: first trimester diagnosis confirmed on cultured amniotic fluid cells and fetal tissues.

Chorionic villi obtained during the first trimester from a pregnancy at risk for Krabbe's disease were shown to have reduced cerebroside-beta-galactosidase (E.C.3.2.1.46) activity using the artificial substrate trinitrophenylaminolauryl galactocerebroside (TNPAL-galactocerebroside). Assay of this enzyme in cultured amniotic fluid cells following amniocentesis, performed at the patient's request confirmed the diagnosis. Termination of pregnancy was performed and subsequent enzyme studies of the fetal tissues were consistent with the diagnosis of Krabbe's disease, thus confirming that chorionic villi can be used for first trimester diagnosis of this condition.

Amniocentesis↗
PubMed1998

A superfamily of metalloenzymes unifies phosphopentomutase and cofactor-independent phosphoglycerate mutase with alkaline phosphatases and sulfatases.

Sequence analysis of the probable archaeal phosphoglycerate mutase resulted in the identification of a superfamily of metalloenzymes with similar metal-binding sites and predicted conserved structural fold. This superfamily unites alkaline phosphatase, N-acetylgalactosamine-4-sulfatase, and cerebroside sulfatase, enzymes with known three-dimensional structures, with phosphopentomutase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, phosphoglycerol transferase, phosphonate monoesterase, streptomycin-6-phosphate phosphatase, alkaline phosphodiesterase/nucleotide pyrophosphatase PC-1, and several closely related sulfatases. In addition to the metal-binding motifs, all these enzymes contain a set of conserved amino acid residues that are likely to be required for the enzymatic activity. Mutational changes in the vicinity of these residues in several sulfatases cause mucopolysaccharidosis (Hunter, Maroteaux-Lamy, Morquio, and Sanfilippo syndromes) and metachromatic leucodystrophy.

Alkaline Phosphatase↗
PubMed2001

Conserved core structure and active site residues in alkaline phosphatase superfamily enzymes.

Cofactor-independent phosphoglycerate mutase (iPGM) has been previously identified as a member of the alkaline phosphatase (AlkP) superfamily of enzymes, based on the conservation of the predicted metal-binding residues. Structural alignment of iPGM with AlkP and cerebroside sulfatase confirmed that all these enzymes have a common core structure and revealed similarly located conserved Ser (in iPGM and AlkP) or Cys (in sulfatases) residues in their active sites. In AlkP, this Ser residue is phosphorylated during catalysis, whereas in sulfatases the active site Cys residues are modified to formylglycine and sulfatated. Similarly located Thr residue forms a phosphoenzyme intermediate in one more enzyme of the AlkP superfamily, alkaline phosphodiesterase/nucleotide pyrophosphatase PC-1 (autotaxin). Using structure-based sequence alignment, we identified homologous Ser, Thr, or Cys residues in other enzymes of the AlkP superfamily, such as phosphopentomutase, phosphoglycerol transferase, phosphonoacetate hydrolase, and GPI-anchoring enzymes (glycosylphosphatidylinositol phosphoethanolamine transferases) MCD4, GPI7, and GPI13. We predict that catalytical cycles of all the enzymes of AlkP superfamily include phosphoenzyme (or sulfoenzyme) intermediates.

Alkaline Phosphatase↗
PubMed2005

The synthesis of internal standards for the quantitative determination of sphingolipids by tandem mass spectrometry.

Novel internal standards have been synthesised for the quantitative determination by tandem mass spectrometry (MS/MS) of the sphingolipids that accumulate in lysosomal storage diseases. The [d4]C16- and [d47]C24-isoforms of galactosylceramide (CMH), lactosylceramide (CDH), globotriaosylceramide (CTH), cerebroside sulphate, sphingomyelin and G(M1)-, G(M2)- and G(M3)-gangliosides were synthesised by the reaction of their lyso-forms with the acid chlorides of hexadecanoic 5,5,6,6-d4 acid ([d4]-palmitic acid) and tetracosanoic-d47 acid ([d47]-lignoceric acid), respectively. The acid chlorides were formed using oxalyl chloride. The structures of the internal standards were confirmed by MS/MS. The fragmentation pattern of each novel compound was similar to that of the corresponding natural form of the sphingolipid, making it a good internal standard for the quantitative determination of the natural sphingolipid by ESI-MS/MS. Characteristic product ions were identified for each compound.

Lysosomal Storage Diseases↗
PubMed1993

Isolation, characterization, and proteolysis of human prosaposin, the precursor of saposins (sphingolipid activator proteins).

Prosaposin contains separate domains in tandem for four saposins, A, B, C, and D. These mature saposins are produced by limited proteolysis of prosaposin. They are involved in lysosomal hydrolysis of GM1 ganglioside, gluco- and galactocerebrosides, sulfatides, and sphingomyelin and other sphingolipids. Prosaposin also exists as a secretory protein in body fluids. In this investigation prosaposin was expressed in Spodoptera frugiperda cells (Sf9) by infection with baculovirus containing a full length cDNA coding for human prosaposin. Prosaposin was isolated and purified from spent culture medium of the recombinant Sf9 cell cultures as well as from human seminal plasma and milk. From sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the molecular weight of both native human prosaposins is estimated to be 66 kDa and that of recombinant prosaposin as 58 kDa. Deglycosylation of native and recombinant prosaposins yielded a protein with a molecular weight of 54 kDa and isoelectric point of 5.4. The N-terminal sequence of both native and recombinant prosaposins was identical (G-P-V-L-L-G-L-K). Like mature saposins, all prosaposins possessed stimulative activity for cerebroside beta-glucosidase (saposins A and C activity), GM1 ganglioside beta-galactosidase (saposin B activity), and sphingomyelinase (saposin D activity) but not sulfatide sulfatase (saposin B activity). Partially proteolyzed products derived from prosaposins were isolated and identified. From seminal plasma, two proteins of 48 and 29 kDa and from Sf9 culture media, two proteins of 39 and 26 kDa were characterized. N-terminal amino acid sequencing and Western blot analysis of each protein indicated that the 39-and 48-kDa proteins are cleavage products containing domains for saposins B, C, and D (trisaposins), and the 26- and 29-kDa proteins are cleavage products containing domains for saposins C and D (disaposin). These observations suggest that proteolysis of prosaposin in these tissues occurs sequentially from the N-terminal region. Proteins involved in the initial proteolysis of prosaposin were partially characterized in human testis.

Amino Acid Sequence↗