Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Sphingolipids”

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 55 records · Page 3Linked to original sources
PubMed1995

Both sphingolipids and cholesterol participate in the detergent insolubility of alkaline phosphatase, a glycosylphosphatidylinositol-anchored protein, in mammalian membranes.

SPB-1, a Chinese hamster ovary cell variant defective in serine palmitoyltransferase activity for sphingolipid synthesis, provides a useful system for studying the effects of sphingolipids and/or cholesterol deprivation on cellular functions and membrane properties. To investigate whether there was an interaction among sphingolipids, cholesterol, and glycosylphosphatidylinositol (GPI)-anchored proteins in biological membranes, we introduced human placental alkaline phosphatase (PLAP) in SPB-1 and in wild type cells by stable transfection and examined the effects of sphingolipid and/or cholesterol deprivation on the solubility of PLAP in Triton X-100. Although the PLAP solubility of the membranes isolated from the control cells in Triton X-100 was only 10%, deprivation of sphingolipid and cholesterol further enhanced the solubility, which reached 50% when both sphingolipids and cholesterol were deprived. The enhanced solubility was suppressed to the control level by metabolic complementation with exogenous sphingosine and cholesterol. The sphingolipid and cholesterol content of the isolated membranes changed independently, eliminating the possibility that sphingolipid deprivation induced a reduction in cellular cholesterol and enhanced PLAP solubility and vice versa. It was also unlikely that the enhanced solubility was due to structural changes in PLAP molecules since, regardless of sphingolipid and cholesterol deprivations, almost all PLAP had the GPI-anchor moiety and there were no differences in the apparent molecular weight of the protein in supernatant and precipitate fractions of the detergent-treated membranes. In addition, the expression level of caveolin in the isolated membranes was not significantly affected by sphingolipids and/or cholesterol depletion. These results indicated that both sphingolipids and cholesterol were involved in the PLAP insolubility and suggested that these lipids coordinately played a role in formation of Triton X-100-resistant complexes.

Acyltransferases↗
PubMed2003

Roles for sphingolipid biosynthesis in mediation of specific programs of the heat stress response determined through gene expression profiling.

Previous studies have demonstrated roles for de novo production of sphingolipids in Saccharomyces cerevisiae in the regulation of the transient cell cycle arrest and nutrient permease degradation associated with the heat stress response, suggesting multiple functions for yeast sphingolipids in this response. We, therefore, sought to determine the generalized involvement of sphingolipids in the heat stress response by using microarray hybridization of RNA isolated from heat-stressed cultures of the mutant strain lcb1-100, which is unable to produce sphingolipids in response to heat. Approximately 70 genes showed differential regulation during the first 15 min of heat stress in the lcb1-100 strain compared with the wild type strain, indicating a requirement for de novo sphingolipid biosynthesis for proper regulation of these genes during heat stress. Grouping these genes into functional categories revealed several pathways, including some in which sphingolipids were previously suspected to play a role, such as stress response pathways and cell cycle regulation. Hierarchical clustering analysis revealed sphingolipid involvement in regulation of tRNA synthesis and metabolic genes and transporters. Additionally, the microarray results demonstrated novel sphingolipid involvement in transcriptional regulation of pathways of translation and cell wall organization and biogenesis. Our results demonstrate a broad-reaching effect of sphingolipids in the yeast heat stress response and suggest that the mechanism of sphingolipid involvement in several cellular pathways occurs via sphingolipid-mediated regulation of message levels.

Amino Acids↗
PubMed1992

Phenotypes of sphingolipid-dependent strains of Saccharomyces cerevisiae.

To study sphingolipid function(s) in Saccharomyces cerevisiae, we have investigated the effects of environmental stress on mutant (SLC) strains (R. C. Dickson, G. B. Wells, A. Schmidt, and R. L. Lester, Mol. Cell. Biol. 10:2176-2181, 1990) that either contain or lack sphingolipids, depending on whether they are cultured with a sphingolipid long-chain base. Strains lacking sphingolipid were unable to grow at low pH, at 37 degrees C, or with high salt concentrations in the medium; these environmental stresses are known to inhibit the growth of some S. cerevisiae strains with a defective plasma membrane H(+)-ATPase. We found that sphingolipids were essential for proton extrusion at low pH and furthermore found that cells lacking sphingolipid no longer exhibited net proton extrusion at normal pH after a 1-min exposure to pH 3. Cells lacking sphingolipid appeared to rapidly become almost completely permeable to protons at low pH. The deleterious effects of low pH could be partially prevented by 1 M sorbitol in the suspension of cells lacking sphingolipid. Proton extrusion at normal pH (pH 6) was significantly inhibited at 39 degrees C only in cells lacking sphingolipid. Thus, the product of an SLC suppressor gene permits life without sphingolipids only in a limited range of environments. Outside this range, sphingolipids appear to be essential for maintaining proton permeability barriers and/or for proton extrusion.

Fungal Proteins↗
PubMed1997

Sphingolipids--the enigmatic lipid class: biochemistry, physiology, and pathophysiology.

The "sphingosin" backbone of sphingolipids was so named by J. L. W. Thudichum in 1884 for its enigmatic ("Sphinx-like") properties. Although still an elusive class of lipids, research on the involvement of sphingolipids in the signal transduction pathways that mediate cell growth, differentiation, multiple cell functions, and cell death has been rapidly expanding our understanding of these compounds. In addition to the newly discovered role of ceramide as an intracellular second messenger for tumor necrosis factor-alpha, IL-1beta, and other cytokines, sphingosine, sphingosine-1-phosphate, and other sphingolipid metabolites have recently been demonstrated to modulate cellular calcium homeostasis and cell proliferation. Perturbation of sphingolipid metabolism using synthetic and naturally occurring inhibitors of key enzymes of the biosynthetic pathways is aiding the characterization of these processes; for examples, inhibition of cerebroside synthase has indicated a role for ceramide in cellular stress responses including heat shock, and inhibition of ceramide synthase (by fumonisins) has revealed the role of disruption of sphingolipid metabolism in several animal diseases. Fumonisins are currently the focus of a FDA long-term tumor study. This review summarizes recent research on (i) the role of sphingolipids as important components of the diet, (ii) the role of sphingoid base metabolites and the ceramide cycle in expression of genes regulating cell growth, differentiation, and apoptosis, (iii) the use of cerebroside synthase inhibitors as tools for understanding the role of sphingolipids as mediators of cell cycle progression, renal disease, and stress responses, and (iv) the involvement of disrupted sphingolipid metabolism in animal disease and cellular deregulation associated with exposure to inhibitors of ceramide synthase and serine palmitoyltransferase, key enzymes in de novo sphingolipid biosynthesis. These findings illustrate how an understanding of the function of sphingolipids can help solve questions in toxicology and this is undoubtedly only the beginning of this story.

Amidohydrolases↗
PubMed1995

Localization of epidermal sphingolipid synthesis and serine palmitoyl transferase activity: alterations imposed by permeability barrier requirements.

Sphingolipids, the predominant lipid species in mammalian stratum corneum play, a central role in permeability barrier homeostatis. Prior studies have shown that the epidermis synthesizes abundant sphingolipids, a process regulated by barrier requirements, and that inhibition of sphingolipid synthesis interferes with barrier homeostasis. To investigate further the relationship between epidermal sphingolipid metabolism and barrier function, we localized sphingolipid synthetic activity in murine epidermis under basal conditions, and following acute (acetone treatment) or chronic (essential fatty acid deficiency, EFAD) barrier perturbation, using dithiothreitol and/or the staphylococcal epidermolytic toxin to isolate the lower from the outer epidermis. Under basal conditions, both the activity of serine palmitoyl transferase (SPT), the rate-limiting enzyme of sphingolipid synthesis, and the rates of 3H-H2O incorporation into sphingolipids were nearly equivalent in the lower and the outer epidermis. Following acute barrier perturbation, SPT activity increased significantly in both the lower (35%; P < 0.05) and the outer epidermal layers (60%; P < 0.01). The rates of 3H-H2O incorporation into each major sphingolipid family, including ceramides, glucosylceramides and sphingomyelin, increased significantly in both the lower and the outer epidermis of treated flanks after acute barrier disruption. Finally, SPT activity was modestly elevated (20%; P < 0.01) in the lower but not in the outer epidermis of EFAD animals. These studies demonstrate the ability of both lower and outer epidermal cells to generate sphingolipids, and that permeability barrier homeostatic mechanisms appear to differentially regulate SPT activity and sphingolipid synthesis in the lower and the outer epidermis in response to acute and chronic barrier perturbation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetone↗
PubMed1993

Sphingolipid breakdown products: anti-proliferative and tumor-suppressor lipids.

The sphingolipids are a family of lipids found ubiquitously in eukaryotic cell membranes. Within the last decade sphingolipids have emerged as active participants in the regulation of cell growth, differentiation, transformation, and cell-cell contact. A prototypic sphingolipid signalling pathway is the 'sphingomyelin cycle,' in which membrane sphingomyelin is hydrolyzed in response to extracellular stimuli, generating the putative second messenger ceramide. Ceramide, in turn, is thought to propagate the signal into the cell interior by the activation of a phosphatase. It is likely that other sphingolipids are components of similar signalling cycles, generating a variety of lipid messengers which participate in as yet undefined pathways. Sphingosine, for example, is a potential breakdown product of all sphingolipids, and is well-known for its pharmacologic inhibition of protein kinase C. However, it is becoming apparent that sphingosine is active in multiple signalling cascades that are independent of protein kinase C, including effects on fibroblast cell growth and the regulation of the retinoblastoma tumor suppressor protein. Similarly, lyso-sphingolipids, while comprising only a minor fraction of the cell's total sphingolipids, are turning out to have biological effects which warrant their investigation as potential signalling molecules. A distinguishing characteristic of sphingolipid breakdown products is their apparent participation in anti-proliferative pathways of cell regulation. Thus, sphingolipid breakdown products can be found to play roles in growth inhibition, induction of differentiation, and programmed cell death. In coordination with other cellular signal transduction pathways, the sphingolipid breakdown products may be the harnesses on cell growth and may also contribute to the suppression of oncogenesis.

Animals↗
PubMed1997

Suppressor gene analysis reveals an essential role for sphingolipids in transport of glycosylphosphatidylinositol-anchored proteins in Saccharomyces cerevisiae.

Sphingolipids are normally necessary for growth of Saccharomyces cerevisiae cells, but mutant strains that bypass the need for sphingolipids have been identified. Such bypass mutants fail to grow under stressful conditions, including low pH (pH 4.1), when they lack sphingolipids. To begin to understand why sphingolipids seem to be necessary for coping with low-pH stress, we screened a genomic library and selected a suppressor gene, CWP2 (cell wall protein 2), that when present in multiple copies partially compensates for the lack of sphingolipids and enhances survival at low pH. To explain these results, we present evidence that sphingolipids are required for a normal rate of transport of glycosylphosphatidylinositol (GPI)-anchored proteins, including Cwp2 and Gas1/Gpg1, from the endoplasmic reticulum (ER) to the Golgi apparatus. The effect of sphingolipids is specific for transport of GPI-anchored proteins because no effect on the rate of transport of carboxypeptidase Y, a non-GPI-anchored protein, was observed. Since the Gasl protein accumulated in the ER with a GPI anchor in cells lacking sphingolipids, we conclude that sphingolipids are not necessary for anchor attachment. Therefore, sphingolipids must be necessary for a step in formation of COPII vesicles or for their transport to the Golgi apparatus. Our data identify the Cwp2 protein as a vital component in protecting cells from the stress of low pH.

Biological Transport↗
PubMed2001

Immunoseparation of sphingolipid-enriched membrane domains enriched in Src family protein tyrosine kinases and in the neuronal adhesion molecule TAG-1 by anti-GD3 ganglioside monoclonal antibody.

Rat cerebellar granule cells differentiated in culture were fed [1-(3)H]sphingosine, allowing the metabolic radiolabelling of all cell sphingolipids and phosphatidylethanolamine. A detergent-insoluble sphingolipid-enriched membrane fraction, containing about 60% of cell sphingolipids, but only trace amounts of phosphatidylethanolamine, was prepared from [1-(3)H]sphingosine-fed cells by sucrose gradient centrifugation. This fraction was enriched in the Src family protein tyrosine kinases c-Src, Lyn and Fyn and in the GPI-anchored neuronal adhesion molecule TAG-1. The cell lysate and the sphingolipid-enriched membrane fraction were subjected to immunoprecipitation with anti-GD3 ganglioside monoclonal antibody R24, under experimental conditions designed to preserve the integrity of the domain. The radioactive lipid composition of the immunoprecipitates obtained from the cell lysate and from the sphingolipid-enriched fraction were very similar, and closely resembled the sphingolipid composition of the whole sphingolipid-enriched membrane fraction. In fact, the immunoprecipitates contained, together with GD3 ganglioside, all cell glycosphingolipids and sphingomyelin, whereas they did not contain phosphatidylethanolamine. Moreover, cholesterol and phosphatidylcholine were detected in the immunoprecipitates by qualitative TLC analysis followed by colourimetric visualization. c-Src, Lyn, Fyn and TAG-1 were associated with the anti-GD3 antibody immunoprecipitate. These proteins were not detected in the immunoprecipitates obtained under experimental conditions different from those designed to preserve the integrity of the domain. These data suggest that a membrane domain containing cholesterol, phosphatidylcholine, sphingolipids and proteins can be separated from the total cell membranes by anti-GD3 antibody immunoprecipitation, and that the association of c-Src, Fyn, Lyn, and TAG-1 with the sphingolipid-enriched domain is mediated by the interaction with a complex lipid environment, rather than by specific interactions with a single sphingolipid species.

Animals↗
PubMed2000

Sli2 (Ypk1), a homologue of mammalian protein kinase SGK, is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast.

ISP-1 is a new type of immunosuppressant, the structure of which is homologous to that of sphingosine. In a previous study, ISP-1 was found to inhibit mammalian serine palmitoyltransferase, the primary enzyme involved in sphingolipid biosynthesis, and to reduce the intracellular pool of sphingolipids. ISP-1 induces the apoptosis of cytotoxic T cells, which is triggered by decreases in the intracellular levels of sphingolipids. In this study, the inhibition of yeast (Saccharomyces cerevisiae) proliferation by ISP-1 was observed. This ISP-1-induced growth inhibition was also triggered by decreases in the intracellular levels of sphingolipids. In addition, DNA duplication without cytokinesis was detected in ISP-1-treated yeast cells on flow cytometry analysis. We have cloned multicopy suppressor genes of yeast which overcome the lethal sphingolipid depletion induced by ISP-1. One of these genes, SLI2, is synonymous with YPK1, which encodes a serine/threonine kinase. Kinase-dead mutants of YPK1 did not show any resistance to ISP-1, leading us to predict that the kinase activity of the Ypk1 protein should be essential for this resistance to ISP-1. Ypk1 protein overexpression had no effect on sphingolipid biosynthesis by the yeast. Furthermore, both the phosphorylation and intracellular localization of the Ypk1 protein were regulated by the intracellular sphingolipid levels. These data suggest that the Ypk1 protein is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. The Ypk1 protein was reported to be a functional homologue of the mammalian protein kinase SGK, which is a downstream kinase of 3-phosphoinositide-dependent kinase 1 (PDK1). PDK1 phosphotidylinositol (PI) is regulated by PI-3,4,5-triphosphate and PI-3,4-bisphosphate through the pleckstrin homology (PH) domain. Overexpression of mammalian SGK also overcomes the sphingolipid depletion in yeast. Taking both the inability to produce PI-3,4, 5-triphosphate and PI-3,4-bisphosphate and the lack of a PH domain in the yeast homologue of PDK1, the Pkh1 protein, into account, these findings further suggest that yeast may use sphingolipids instead of inositol phospholipids as lipid mediators.

Fatty Acids, Monounsaturated↗
PubMed2004

Modulation of amyloid precursor protein cleavage by cellular sphingolipids.

Lipid rafts and their component, cholesterol, modulate the processing of beta-amyloid precursor protein (APP). However, the role of sphingolipids, another major component of lipid rafts, in APP processing remains undetermined. Here we report the effect of sphingolipid deficiency on APP processing in Chinese hamster ovary cells treated with a specific inhibitor of serine palmitoyltransferase, which catalyzes the first step of sphingolipid biosynthesis, and in a mutant LY-B strain defective in the LCB1 subunit of serine palmitoyltransferase. We found that in sphingolipid-deficient cells, the secretion of soluble APPalpha (sAPPalpha) and the generation of C-terminal fragment cleaved at alpha-site dramatically increased, whereas beta-cleavage activity remained unchanged, and the epsilon-cleavage activity decreased without alteration of the total APP level. The secretion of amyloid beta-protein 42 increased in sphingolipid-deficient cells, whereas that of amyloid beta-protein 40 did not. All of these alterations were restored in sphingolipid-deficient cells by adding exogenous sphingosine and in LY-B cells by transfection with cLCB1. Sphingolipid deficiency increased MAPK/ERK activity and a specific inhibitor of MAPK kinase, PD98059, restored sAPPalpha level, indicating that sphingolipid deficiency enhances sAPPalpha secretion via activation of MAPK/ERK pathway. These results suggest that not only the cellular level of cholesterol but also that of sphingolipids may be involved in the pathological process of Alzheimer's disease by modulating APP cleavage.

Amyloid beta-Protein Precursor↗
PubMed2002

Dietary sphingolipids in colorectal cancer prevention.

Sphingolipids are widespread membrane components that are found in all eukaryotic cells. They consist of a long chain sphingoid-base, usually sphingosine, which is acylated at the 2-amino position, forming a ceramide. All together, sphingolipids may represent the most structurally diverse category of lipids in nature. There is no known nutritional requirement for sphingolipids. Nonetheless, studies with experimental animals have shown that consumption of sphingolipids inhibits colon carcinogenesis, reduces serum low-density lipoprotein cholesterol and elevates high-density lipoproteins, which suggest that they are 'functional' components of food. In animal models (CF1 mice) sphingomyelin supplementation reduces the number of aberrant colonic crypt foci by approximately 70% and, with longer feeding, reduces the number of colonic adenocarcinomas. A possible mechanism of action of sphingolipids in suppressing colon carcinogenesis is that exogenously supplied sphingolipids bypass a sphingolipid signalling defect that is important in cancer (for example, a loss of cellular sphingomyelin turnover to produce ceramide and sphingosine). Indirect evidence suggests that sphingolipids can inhibit colon cancer in humans: sphingosine and ceramide induce apoptosis in a human adenocarcinoma cell line and feeding sphingolipids to Min mice reduces the number of colon tumours.

Adenocarcinoma↗
PubMed2005

Sphingolipids in infectious diseases.

Sphingolipids are ubiquitous constituents of membrane lipids in eukaryotes. Sphingolipid metabolites modulate various cellular events including proliferation, differentiation, and apoptosis. In addition, sphingolipids, along with cholesterol, form detergent-resistant membrane microdomains, so called 'lipid-rafts', which are implicated in signal transduction and membrane trafficking. Sphingolipids are also relevant to infectious diseases. Various types of pathogens exploit the sphingolipids of host cells as membrane receptors. Sphingolipid metabolites regulate pathogen infection and host defense: for instance, a specific glycosphingolipid acts as an endogenous ligand for activation of natural killer T cells. Lipid-rafts of host cells serve as platforms also for infection signaling and entry of intracellular parasites. Moreover, some post-infectious autoimmune diseases result from production of antibodies cross-reacting with mammalian sphingolipids. Differences in the pathways of sphingolipid metabolism between mammals and non-mammals are good clues for rational development of new anti-infectious disease drugs. This review summarizes recent advances in sphingolipid biology related to infectious diseases.

Bacterial Toxins↗
PubMed2006

Sphingolipid-binding proteins.

Emerging information on sphingolipid metabolism and signaling is leading to a better understanding of cellular processes such as apoptosis, cancer, cell survival and aging. In this review, we discuss the involvement of sphingolipids in these processes and focus on underlying mechanisms based on sphingolipid:protein interactions. Due to the inherent difficulty of studying lipids, we discuss techniques that are useful in the elucidation of these interactions. We classify sphingolipid-binding proteins into four main classes: receptor, effector, enzyme, and transporter. Known structures of sphingolipid-binding proteins are surveyed, and sphingolipid-binding characteristics are described, acknowledging the limitations that there are presently insufficient protein:sphingolipid complexes for more definitive conclusions on this topic. Finally we summarize relevant literature to better inform the reader about sphingolipid:protein interactions.

Animals↗
PubMed2004

Sphingolipids as coenzymes in anion transfer and tumor death.

Many kinds of natural sphingolipids and their analogs stimulate or inhibit a wide assortment of biochemical phenomena and enzymes. The puzzle considered here is: how can these lipids control so many different kinds of processes? In almost every study in which a structural comparison was made, an allylic alcohol moiety [-CH=CH-CH(OH)-] was found to be an essential feature of the sphingolipid. Many of those stimulations lead to cell death, emphasizing the importance of allylic sphingolipid structure in the design of chemotherapeutic agents. The proposal offered here is that these lipids function as coenzymes, in which the allylic moiety acts as an anion transferring agent, forming transient phosphate or acyl or peptidyl esters for the synthesis or hydrolysis of phosphoproteins, proteins, and phospholipids. Sphingolipids that inhibit these reactions may simply displace the active sphingolipids from their sites in the enzymes' active regions, or bind to the enzymes' allosteric region. This kind of competition could act as a major homeostatic control mechanism. Some of the allylic sphingolipids also generate reactive oxygen, possibly by oxidation of the allylic alcohol group. This explains the need to control redox-controlling metabolites in sphingolipid-controlled processes (e.g., glutathione). Many anticancer drugs that produce apoptosis in tumors possess an allylic alcohol residue, affect protein phosphorylation, and produce reactive oxygen species. They may be therapeutically useful because they control the action of sphingolipids as anion transfer agonists or inhibitors.

Anions↗
PubMed2000

Different sphingolipids show differential partitioning into sphingolipid/cholesterol-rich domains in lipid bilayers.

Two fluorescence-based approaches have been applied to examine the differential partitioning of fluorescent phospho- and sphingolipid molecules into sphingolipid-enriched domains modeling membrane "lipid rafts." Fluorescence-quenching measurements reveal that N-(diphenylhexatrienyl)propionyl- (DPH3:0-)-labeled gluco- and galactocerebroside partition into sphingolipid-enriched domains in sphingolipid/phosphatidylcholine/cholesterol bilayers with substantially higher affinity than do analogous sphingomyelin, ceramide, or phosphatidylcholine molecules. By contrast, the affinity of sphingomyelin and ceramide for such domains is only marginally greater than that of a phosphatidylcholine with similar hydrocarbon chains. By using direct measurements of molecular partitioning between vesicles of different compositions, we show that the relative affinities of different C(6)-NBD- and C(5)-Bodipy-labeled sphingolipids for sphingolipid-enriched domains are quantitatively, and in most circumstances even qualitatively, quite different from those found for species whose N-acyl chains more closely resemble the long saturated chains of cellular sphingolipids. These findings lend support in principle to previous suggestions that differential partitioning of different sphingolipids into "raft" domains could contribute to the differential trafficking of these species in eukaryotic cells. However, our findings also indicate that short-chain sphingolipid probes previously used to examine this phenomenon are in general ill-suited for such applications.

Cholesterol↗
PubMed1999

Yeast sphingolipids.

Many advances in our understanding of fungal sphingolipids have been made in recent years. This review focuses on the types of sphingolipids that have been found in fungi and upon the genes in Saccharomyces cerevisiae, the common baker's yeast, that are necessary for sphingolipid metabolism. While only a small number of fungi have been examined, most contain sphingolipids composed of ceramide derivatized at carbon-1 with inositol phosphate. Further additions include mannose and then other carbohydrates. The second major class of fungal sphingolipids is the glycosylceramides, having either glucose or galactose attached to ceramide rather than inositol phosphate. The glycosylceramides sometimes contain additional carbohydrates. Knowledge of the genome sequence has expedited identification of S. cerevisiae genes necessary for sphingolipid metabolism. At least one gene is known for most steps in S. cerevisiae sphingolipid metabolism, but more are likely to be identified so that the 13 known genes are likely to grow in number. The AUR1 gene is necessary for addition of inositol phosphate to ceramide and has been identified as a target of several potent antifungal compounds. This essential step in yeast sphingolipid synthesis, which is not found in humans, appears to be an excellent target for the development of more effective antifungal compounds, both for human and for agricultural use.

Amino Acid Sequence↗
PubMed2000

Mixed membranes of sphingolipids and glycerolipids as studied by spin-label ESR spectroscopy. A search for domain formation.

The temperature dependences of the ESR spectra from different positional isomers of sphingomyelin and of phosphatidylcholine spin-labeled in their acyl chain have been compared in mixed membranes composed of sphingolipids and glycerolipids. The purpose of the study was to identify the possible formation of sphingolipid-rich in-plane membrane domains. The principal mixtures that were studied contained sphingomyelin and the corresponding glycerolipid phosphatidylcholine, both from egg yolk. Other sphingolipids that were investigated were brain cerebrosides and brain gangliosides, in addition to sphingomyelins from brain and milk. The outer hyperfine splittings in the ESR spectra of sphingomyelin and of phosphatidylcholine spin-labeled on C-5 of the acyl chain were consistent with mixing of the sphingolipid and glycerolipid components, in fluid-phase membranes. In the gel phase of egg sphingomyelin and its mixtures with phosphatidylcholine, the outer hyperfine splittings of sphingomyelin spin-labeled at C-14 of the acyl chain of sphingomyelin are smaller than those of the corresponding sn-2 chain spin-labeled phosphatidylcholine. This is in contrast to the situation with sphingomyelin and phosphatidylcholine spin-labeled at C-5, for which the outer hyperfine splitting is always greater for the spin-labeled sphingomyelin. The behavior of the C-14 spin-labels is attributed to a different geometry of the acyl chain attachments of the sphingolipids and glycerolipids that is consistent with their respective crystal structures. The two-component ESR spectra of sphingomyelin and phosphatidylcholine spin-labeled at C-14 of the acyl chain directly demonstrate a broad two-phase region with coexisting gel and fluid domains in sphingolipid mixtures with phosphatidylcholine. Domain formation in membranes composed of sphingolipids and glycerolipids alone is related primarily to the higher chain-melting transition temperature of the sphingolipid component.

Electron Spin Resonance Spectroscopy↗
PubMed1998

Sphingolipids and cell signalling.

The sphingolipid storage disorders constitute a group of inherited metabolic disorders in which the structure of the stored sphingolipid and the corresponding genetic defect have been established. However, the pathological mechanism(s) behind the disorders has not been fully elucidated. Sphingolipids are known to be recognition molecules involved in intercell communication and altered expression might lead to dyscommunication. The impaired degradation and lysosomal accumulation of specific sphingolipids might influence the metabolism of other molecules and/or intracellular transport, which in turn might alter the distribution of these molecules. However, the progress of these diseases indicates that additional factors, besides the stored sphingolipid itself, might be involved. During the last decade, several sphingolipids have emerged as active participants in intracellular signalling processes such as growth control and apoptosis. Particular interest focused on the sphingolipid metabolites, ceramide and sphingosine, as potential mediators in intracellular events and an altered presence of these metabolites in sphingolipidoses cannot be ruled out. Some sphingolipids have been found to influence cytokine release and thereby might induce immunological processes, which are known to exist in at least one of the sphingolipidoses--Gaucher disease. These processes might already have a pathogenic effect during early development, before significant storage has occurred.

Animals↗