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At least 703 records · Page 39Linked to original sources
PubMed2000

Implication of sphingolipid metabolism in the stability of the Golgi apparatus.

We examined the effects of short chain and long chain ceramides on the stability of the Golgi apparatus. Short chain ceramides, C(2)- and C(6)-ceramides, blocked brefeldin A-induced Golgi disassembly without affecting the rapid release of Golgi coat proteins, whereas they did not inhibit brefeldin A-induced tubulation of endosomes. Both short chain ceramides also retarded Golgi disassembly induced by nordihydroguaiaretic acid and nocodazole, suggesting that they stabilize the Golgi apparatus. In contrast to short chain ceramides, natural long chain ceramides, when incorporated into cells or formed within cells upon treatment with sphingomyelinase or metabolic inhibitors, enhanced brefeldin A-induced Golgi disassembly. These results suggest that sphingolipid metabolism is implicated in the stability of the Golgi apparatus.

Animals↗
PubMed1999

Isolation and structural determination of new sphingolipids and pharmacological activity of africanene and other metabolites from Sinularia leptoclados.

Two new sphingolipids, (2S,3S,4R)-1,3,4-trihydroxy-2-[((R)-2'-hydroxytetradecanoyl) amino] tricosane (4) and (2S,3S,4R)-1,3,4-triacetoxy-2-[((R)-2'-acetoxyoctadecanoyl) amino]octadecane (5) along with africanene (1, reasonably good yield), 23-demethylgargosterol (2) and batylalcohol (3) have been isolated from the soft coral Sinularia leptoclados. Preliminary studies for pharmacological activity (blind screening and toxicity studies) of africanene were conducted. Africanene exhibited in vitro and in vivo cytotoxicity, dose dependent hypotensive activity as well as antiinflammatory activity. The pharmacological and toxicity studies on africanene are being reported for the first time and findings strongly encourage further investigation. Compounds 1, 4 and 5 were studied for the antibacterial, antifungal and antiviral activity while compounds 4 and 5 were also studied for the short term in vitro cytotoxic activity.

Animals↗
PubMed2002

Novel sphingolipids from Conyza canadensis.

New sphingolipids, 1,3,5-trihydroxy-2-hexadecanoylamino-(6E,9E)-heptacosdiene (1). 1,3,5-trihydroxy-2-hexadecanoylamino-(6E,9E)-heptacosdiene-1-O-glucopyranoside (2). 1,3-dihydroxy-2-hexanoylamino-(4E)-heptadecene (3). have been isolated from Conyza canadensis, along with five known compounds, p-hydroxybenzoic acid, 3,5-dihydroxybenzoic acid, 3,5-dimethoxybenzoic acid, 3beta-hydroxyolean-12-en-28-oic acid, and 3beta-erythrodiol, isolated for the first time from this species. Their structures were determined by spectroscopic methods ((1)H- and (13)C-NMR, IR and MS) and two dimensional (2D)-NMR experiments.

Conyza↗
PubMed2001

Glucosylceramide synthesis inhibitors block pharmacologically induced dispersal of the Golgi and anterograde membrane flow from the endoplasmic reticulum: implication of sphingolipid metabolism in maintenance of the Golgi architecture and anterograde membrane flow.

PDMP (D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol) and PPMP (D,L-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol), inhibitors of glucosylceramide synthesis, blocked brefeldin A (BFA)- and nordihydroguaiaretic acid-induced dispersal of the Golgi and trans Golgi network, and Golgi-derived vesicles were retained in the juxtanuclear region. PDMP and PPMP did not stabilize microtubules but blocked nocodazole-induced extensive fragmentation and dispersal of the Golgi, and large Golgi vesicles were retained in the juxtanuclear region. PPMP is a stronger inhibitor of glucosylceramide synthesis than PDMP, but PDMP showed a stronger activity against BFA-induced retrograde membrane flow. However, PPMP showed a stronger activity for Golgi disruption and inhibition of anterograde trafficking from the endoplasmic reticulum, and rebuilding of the Golgi architecture. Cumulatively, these results suggest that sphingolipid metabolism is implicated in maintenance of the Golgi architecture and anterograde membrane flow from the endoplasmic reticulum but not in Golgi dispersal induced by BFA.

Adenosine Triphosphate↗
PubMed2001

A role for G protein-coupled lysophospholipid receptors in sphingolipid-induced Ca2+ signaling in MC3T3-E1 osteoblastic cells.

Sphingolipids have been proposed to modulate cell function by acting as intracellular second messengers and through binding to plasma membrane receptors. Exposure of MC3T3-E1 osteoblastic cells to sphingosine (SPH), sphingosine-1-phosphate (SPP), or sphingosylphosphorylcholine (SPC) led to the release of Ca2+ from the endoplasmic reticulum (ER) and acute elevations in cytosolic-free Ca2+ ([Ca2+]i). Desensitization studies suggest that SPP and SPC bind plasma membrane endothelial differentiation gene (Edg) receptors for lysophosphatidic acid (LPA). Consistent with the coupling of Edg receptors to G proteins, SPP- and SPC-induced Ca2+ signaling was inhibited by pretreatment of the cells with pertussis toxin (PTx). Of the Edg receptors known to bind SPH derivatives in other cell types, MC3T3-E1 cells were found to express transcripts encoding Edg-1 and Edg-5 but not Edg-3, Edg-6, or Edg-8. In contrast to SPP and SPC, the ability of SPH to elicit [Ca2+]i elevations was affected neither by prior exposure of cells to LPA nor by PTx treatment. However, LPA-induced Ca2+ signaling was blocked in MC3T3-E1 cells previously exposed to SPH. Elevations in [Ca2+]i were not evoked by SPP or SPC in cells treated with 2-aminoethoxydiphenylborate (2-APB), an inhibitor of inositol 1,4,5-trisphosphate (IP3)-gated Ca2+ channels in the ER. No effect of 2-APB was observed on SPH-or LPA-induced [Ca2+]i elevations. The data support a model in which SPP and SPC bind Edg-1 and/or Edg-5 receptors in osteoblasts leading to the release of Ca2+ from the ER through IP3-gated channels.

3T3 Cells↗
PubMed2001

Stimulation of acid sphingomyelinase activity by lysosomal lipids and sphingolipid activator proteins.

Acid sphingomyelinase is a water-soluble, lysosomal glycoprotein that catalyzes the degradation of membrane-bound sphingomyelin into phosphorylcholine and ceramide. Sphingomyelin itself is an important component of the extracellular leaflet of various cellular membranes. The aim of the present investigation was to study sphingomyelin hydrolysis as a membrane-bound process. We analyzed the degradation of sphingomyelin by recombinant, highly purified acid sphingomyelinase in a detergent-free, liposomal assay system. In order to mimic the in vivo intralysosomal conditions as closely as possible a number of negatively charged, lysosomally occuring lipids including bis(monoacylglycero)phosphate and phosphatidylinositol were incorporated into substrate-carrying liposomes. Dolichol and its phosphate ester dolicholphosphate were also included in this study. Bis(monoacylglycero)phosphate and phosphatidylinositol were both effective stimulators of sphingomyelin hydrolysis. Dolichol and dolicholphosphate also significantly increased sphingomyelin hydrolysis. The influence of membrane curvature was investigated by incorporating the substrate into small (SUVs) and large unilamellar vesicles (LUVs) with varying mean diameter. Degradation rates were substantially higher in SUVs than in LUVs. Surface plasmon resonance experiments demonstrated that acid sphingomyelinase binds strongly to lipid bilayers. This interaction is significantly enhanced by anionic lipids such as bis(monoacylglycero)phosphate. Under detergent-free conditions only the sphingolipid activator protein SAP-C had a pronounced influence on sphingomyelin degradation in both neutral and negatively charged liposomes, catalyzed by highly purified acid sphingomyelinase, while SAP-A, -B and -D had no noticeable effect on sphingomyelin degradation.

Dolichols↗
PubMed1987

N-terminal amino-acid sequence of a sphingolipid activator protein missing in a new human Gaucher disease variant.

A naturally occurring non-enzymic sphingolipid activator protein (A1a activator) shown previously to be immunochemically not detectable in a new variant of human Gaucher disease (glucosylceramide-lipidosis) without glucosylceramidase deficiency was characterized by partial sequence analysis. The N-terminal amino-acid sequence of the A1a activator--a glycoprotein with high carbohydrate content--could be determined up to position 38. About 20% of the polypeptide chain are shorter by two amino-acid residues at the N-terminal end. Position 22 seems to be occupied by a carbohydrate-binding asparagine. The N-terminus of the A1a activator does not show any homology with the activator for the enzymic sulfatide degradation.

Amino Acid Sequence↗
PubMed1986

Orientation measurements on ordered multibilayers of phospholipids and sphingolipids from synthetic and natural origin by ATR Fourier transform infrared spectroscopy.

Fourier-transform infrared spectroscopy was applied to natural and synthetic planar membrane multibilayer systems made from phospholipids and sphingolipids to perform orientational measurements utilizing the attenuated total reflectance technique. Applying polarized infrared light, the dichroic ratios and the positions of the peak maxima of various infrared-active bands in dependence on temperature and degree of hydration as well as the phase behaviour were studied. Under certain assumptions - which are discussed - made for the order parameter S, the orientation of various functional groups with respect to the molecular axis or to the membrane normal can be determined. For the gel phase values for S between 0.80 +/- 0.05 for the complete molecule and 0.40 +/- 0.05 for the end methyl group and for the liquid crystalline phase a value of 0.50 +/- 0.05 were approximated. Applying these data, a relatively precise determination of the angles of the oscillating dipole moments of various functional groups could be performed, which - for some vibrations - deviate considerably from those angles assumed earlier. Regarding the phase behaviour, it was found that not only the degree of hydration but the amount of bulk water of the sample has a strong influence on the phase transition temperature Tc (lyotrophism), but only a weak influence on the orientational data.

Fourier Analysis↗
PubMed2005

Analysis of phospho- and sphingolipids in dairy products by a new HPLC method.

Dairy phospho- and sphingolipids are gaining interest due to their nutritional and technological properties. A new HPLC method, using an evaporative laser light-scattering detector, was developed, which enabled excellent separation of glucosylceramide, lactosylceramide, phosphatidic acid, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine, sphingomyelin, and lysophosphatidylcholine in less than 21 min, including the regeneration of the column. No loss of column performance was observed after 1500 runs because an acid buffer was used. The output signal of the evaporative laser light scattering detector was highly dependent of the flow of the carrier gas and the temperature of the nebulizer, and was maximized by means of a response surface experimental design. Finally, raw milk, cream, butter, buttermilk, Cheddar whey, quarg, and Cheddar cheese were analyzed for their polar lipid content. The absolute values varied substantially (0.018 to 0.181 g/100 g of product). Significant differences were found in the relative content of each polar lipid class among the analyzed products.

Animals↗
PubMed2001

Sphingolipid derivatives modulate intracellular Ca2+ in rat synaptosomes.

Sphingosylphosphorylcholine (SPC) induces a rapid increase of intracellular Ca2+ concentration in isolated synaptosomes. This effect is dose-dependent and is also dependent on extracellular Ca2+. Sphingosine (SPH) has a smaller effect and treatment with psychosine (PSY) is ineffective, which suggests that phosphorylation of the 1-carbon of SPH is required for the SPC to act as a Ca2+ release agonist in synaptosomes. Experiments performed in the presence of heparin or ryanodine indicate that SPC-elicited Ca2+ release is not mediated by IP3 or ryanodine receptors. Finally, our results show that the effect of SPC on Ca2+ concentration is nimodipine-sensitive, suggesting that SPC possibly activates a specific sphingolipid-gated Ca2+ channel in synaptosomes.

Animals↗
PubMed1998

Inhibition of fungal sphingolipid biosynthesis by rustmicin, galbonolide B and their new 21-hydroxy analogs.

The mode of action of the known antifungal macrolides rustmicin (1) and galbonolide B (2) has been determined to be the inhibition of sphingolipid biosynthesis. A large scale fermentation and isolation process was developed for production of large quantities of rustmicin. New 21-hydroxy derivatives of both compounds were isolated from pilot scale fermentations and were also produced by biotransformation of rustmicin and galbonolide B.

Antifungal Agents↗
PubMed2000

Sphingolipids of transplantable rat nephroma-RA.

Contents of sphingolipids (ceramide, sphingomyelin, gangliosides) and the composition of their sphingoid bases were studied in the transplantable rat nephroma-RA and in rat kidneys. The content of sphingomyelin was about 1.3-fold decreased and the content of ceramide was about 1.4-fold increased in the nephroma compared to normal kidneys, and this correlated with a 1.4-fold increased activity of neutral sphingomyelinase; however, the activity of the acidic isoform of the enzyme was virtually unchanged. The content of gangliosides was also increased in the nephroma. Ceramide and sphingomyelin of the nephroma, in addition to sphingosine, contained a significant amount of sphinganine, although a considerable amount of the latter was also found in the renal ceramide. The ratio sphingosine/sphinganine in sphingomyelins changed from 65:1 in kidneys to 5:1 in the nephroma. Thus, the biosynthesis of sphingoid bases seems to be disturbed in the transplantable rat nephroma-RA compared to normal kidneys.

Animals↗
PubMed1975

[Investigations on the structure of the sphingolipids of the genus Bacteroides (author's transl)].

In 1972 Fritsche and Thelen have described the difference between the structure of the komplex lipids of the genus Bacteroides and the genus Sphaerophorus. Further investigations of Fritsche demonstrated the possibility of grouping gramnegative anaerobes into the genus Bacteroides in spite of the fact, that one of the final products of metabolism of these strains is butyric acid. These strains are the so-called butyric acid producing Bacteroides. This paper describes the structure of the still unknown fatty acids of the komplex lipids of Bacteroides strains and confirms the heterogenity of the sphingosine bases of Bacteroides as a principle. Fife strains of Bacteroides - with and without production of butyric acid - were used for purification of their long chain bases, which were characterized by degradation. The unknown fatty acids were isolated from B. thetaiotaomicron and analyzed by Dr. Rosenfelder with the aid of mass spectrometry, O-methylation and dehydratisation. The experiments of Rosenfelder demonstrate, that the unknown fatty acids have the behaviour of 3-hydroxy fatty acids, the two main peaks are a hexadecanoic and a heptade-behaviour of 3-hydroxy fatty acids, the two main peaks are a hexadecanoic and a heptadecanoic acid. They have an identical behaviour with the 3-hydroxy-15-methyl-palmitic acid of Myxococcus fulvus. Therefore the genus Bacteroides differs from the genus Sphaerophorus by synthesis of 3-hydroxy fatty acids. The production of sphingolipids is a common characteristic of the genus Bacteroides, each of the five strains demonstrated a heterogeneous pattern of bases with sphingosines with 16 to 20, perhaps also 12 to 14 carbon atoms, sometimes predominantly the branched and n-heptadeca- and the octadeca-sphinganine can be identified. The possibility of the production of phyto-sphingosines is discussed.

Bacteroides↗
PubMed1992

Sphingolipid transport in mitotic HeLa cells.

Mitotic and interphase HeLa cells were labeled with [3H]serine. Ceramide and its derivatives, lactosylceramide and sphingomyelin, were biosynthetically labeled under both conditions. Only in the absence of nocodazole, as the cells entered telophase, was an additional glycosphingolipid synthesized which was identified as GA2 (GalNAc(beta 1,4)Gal(beta 1,4)Glc(beta 1,1)Cer). Ceramide, the basic sphingolipid precursor, is synthesized in the endoplasmic reticulum, whereas its immediate derivatives are synthesized in early Golgi compartments. Transport of newly synthesized proteins from the endoplasmic reticulum to the Golgi is inhibited in mitotic cells while ceramide acquires early Golgi modifications under the same conditions, suggesting that ceramide can be delivered to the Golgi by a different route. Since GA2 is synthesized in late Golgi, its absence in mitotic cells strongly argues for an in vivo inhibition of intra-Golgi transport, an observation with important implications for the mechanism of Golgi division.

Biological Transport↗
PubMed2003

Sphingolipid profile in the CNS of the twitcher (globoid cell leukodystrophy) mouse: a lipidomics approach.

Globoid cell leukodystrophy (Krabbe disease) is caused by mutations in galactosylceramidase, a lysosomal enzyme that acts to digest galactosylceramide, a glycolipid concentrated in myelin, and psychosine (galactosylsphingosine). Globoid cell leukodystrophy has been identified in many species including humans and twitcher mice. Several studies on human tissue have examined the lipid profile in this disease by gas, liquid or thin layer chromatography. Electrospray ionization tandem mass spectrometry combined with reverse phase HPLC has become a powerful alternative strategy, used here to compare the sphingolipid profile of pons/medulla tissue from twitcher mice with control tissue. In this lipidomics LC-MS approach, we scanned for precursors of m/z 264 to obtain a semi-quantitative profile of ceramides and galactosylceramides. Sphingosine-1-phosphate, C18:0 ceramide, C22:0 ceramide and C24:0 ceramide levels were reduced in the pons/medulla of twitcher mice compared to levels in control mice at 31 and 35-37 days of age. The levels of C22:0 and C24:0 galactosylceramide were similar between twitcher and control specimens and there was a trend toward reduced levels of C24:1 galactosylceramide and C24:1 hydroxy-galactosylceramide in twitcher specimens. Psychosine, C 16:0 ceramide and C 18:0 galactosylceramide levels were increased in the CNS of twitcher mice compared to levels in control mice. These data indicate that there is a trend toward decreased levels of long chain fatty acids and increased levels of shorter chain fatty acids in galactosylceramides and ceramides from twitcher mice compared with control mice, and such changes may be due to demyelination characteristic of acute pathology.

Animals↗
PubMed2003

[Sphingolipid signaling: a potential pathway for TNF-alpha induced preconditioning].

Although cytokine activation has long been recognized to associate with cardiac ischemia and reperfusion, the concept that these cytokines may enhance some cardioprotective mechanisms has only recently been considered. Ischemic preconditioning is a biologic phenomenon that activates innate cytoprotective programs in the heart. Ischemic preconditioning has been described where a transient non-lethal ischemic "trigger" or endogenous molecules produced/released by ischemia enables the tissue to become more resistant/tolerant to subsequent potentially lethal ischemia. The mechanisms and signalling events involved in this cytoprotective program still remain obscure. Recently, it has been suggested that cytokine activation including tumour necrosis factor (TNF alpha) may play a key role in the preconditioned phenotype. Moreover, new studies have given the evidence that the exploration of cytokine-activated sphingolipid signalling pathways may enhance our understanding of the preconditioning program.

Ceramides↗
PubMed2006

Regulatory roles of cell surface sialylation in sphingolipid-induced cell death in human B cell lymphoma.

Sphingolipid metabolites are important regulators of cell growth and death. In the present study, we examined the function of cell surface sialic acid in exogenous sphingosine-1-phosphate (S-1-P) or sphingosine-induced cell death. HBL-2 human diffuse large B cell lymphoma cells were incubated with or without Vibrio Cholerae neuraminidase followed by S-1-P or sphingosine. Flow cytometric analysis using Limax flavus agglutinin, a sialic acid-specific lectin, showed that sialylated glycoconjugates are present on the surface of HBL-2 cells and that they were removed by neuraminidase. In addition, the pretreatment with neuraminidase enhanced S-1-P- and sphingosine-induced cell death, an effect that was not dependent on caspase activation. Furthermore, the cell death induced by S-1-P and sphingosine was morphologically distinct from apoptosis. We further examined S-1-P-induced cell death in two clones of HBL-8 Burkitt lymphoma cells with different amounts of cell surface sialic acid. Clone 3G3, which is hypersialylated, was less sensitive to S-1-P than the 3D2 clone, which is hyposialylated, suggesting that the extent of surface sialylation influences the sensitivity to S-1-P. In conclusion, S-1-P and sphingosine induce cell death, and the sensitivity of human B lymphoma cells to these agents appears to depend on the amount of sialic acid on their cell surfaces.

Agglutinins↗
PubMed1990

Modulation of sphingolipid biosynthesis in primary cultured neurons by long chain bases.

Sphingolipid biosynthesis was studied in cultured murine cerebellar cells in the absence and presence of exogenous sphingosine homologues with different alkyl chain lengths (12, 18, and 24 carbon atoms). Labeling of cells with [14C]serine for 24 h indicated that endogenous sphingosine biosynthesis with incorporation of radiolabeled serine was inhibited by these long chain bases (0.5-50 microM) in a concentration-dependent manner; the inhibition was fully reversible after removal of the long chain bases from the culture medium. Metabolic labeling of neurons with [14C]galactose provided strong evidence that the cells were able to use the exogenous sphingosine homologues, irrespective of their alkyl chain length, as substrates for the biosynthesis of glycosphingolipids. When the biosynthetically inert sphingoid, azidosphingosine (5-50 microM), was fed to the cells, de novo sphingosine and glycosphingolipid biosynthesis were both strongly inhibited.

Animals↗