Number Of Glycosphingolipids Research Articles

Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells.

Type 1 diabetes (T1DM) is a chronic autoimmune disease, with a strong genetic background, leading to a gradual loss of pancreatic beta-cells, which secrete insulin and control glucose homeostasis. Patients with T1DM require life-long substitution with insulin and are at high risk for development of severe secondary complications. The incidence of T1DM has been continuously growing in the last decades, indicating an important contribution of environmental factors. Accumulating data indicates that sphingolipids may be crucially involved in T1DM development. The serum lipidome of T1DM patients is characterized by significantly altered sphingolipid composition compared to nondiabetic, healthy probands. Recently, several polymorphisms in the genes encoding the enzymatic machinery for sphingolipid production have been identified in T1DM individuals. Evidence gained from studies in rodent islets and beta-cells exposed to cytokines indicates dysregulation of the sphingolipid biosynthetic pathway and impaired function of several sphingolipids. Moreover, a number of glycosphingolipids have been suggested to act as beta-cell autoantigens. Studies in animal models of autoimmune diabetes, such as the Non Obese Diabetic (NOD) mouse and the LEW.1AR1-iddm (IDDM) rat, indicate a crucial role of sphingolipids in immune cell trafficking, islet infiltration and diabetes development. In this review, the up-to-date status on the findings about sphingolipids in T1DM will be provided, the under-investigated research areas will be identified and perspectives for future studies will be given.

Structure and Biological Activity of Glycosphingolipids from Starfish and Feather Stars

Glycosphingolipids (GSLs) are contained in a various cell membranes and have recently been implicated in many physiologic functions. They are classified based on their sugar moieties into ceramides, cerebrosides, sulfatides, ceramide-oligohexosides, globosides, and gangliosides. A number of GSLs have been obtained from marine invertebrates such as echinoderms, poriferans, and mollusks and have unique biological activities. During the course of our search for biologically active GSLs from echinoderms, we conducted the isolation and structural elucidation of GSLs from starfish and feather stars and found numerous GSLs, some of which have unique structures. In particular, gangliosides from feather stars were unique in that the sialic acids bind to inositol-phosphoceramide. We also found that the GSLs from starfish and feather stars possess neuritogenic activity toward the rat pheochromocytoma cell line PC12, antihyperglycemic effects against type 2 diabetic BKS. Cg-m+/+Leprdb/J (db/db) mice, and antiosteoporosis effects toward the osteoporosis model mice (OVX mice). These biological activities are thought to be related to dementia, osteoporosis, and diabetes, which are becoming social problems, and are expected to become the seeds of preventive or therapeutic drugs for these illness.

Isolation and Structure Determination of Three New Ceramides from the Starfish Distolasterias nipon.

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Isolation and Structure Determination of Three New Ceramides from the Starfish Distolasterias nipon

Starfishes have been reported to contain a number of glycosphingolipids and sterol compounds with unconventional side chain. Some glycosphingolipids have exhibited cytotoxicity, histidine decarboxylate inhibition, DNA topoisomerase I inhibition, moderate wound-healing activity and induced apoptotic DNA damage and cell death in mammalian cell lines. In our search for biologically active and structurally novel lipids from marine organisms, we recently isolated mixtures of several sphingolipids from the starfish Distolasterias nipon collected off the coast of East Sea, Korea. Further HPLC of the fraction resulted in the purification of three new ceramides which are composed of the aglycone part of glycosphingolipids. In this paper we report the isolation and structure determination of new ceramides (compound 1, 2, and 3) isolated from the starfish D. nipon. Compound 1 was isolated as a white amorphous solid which determined for C35H65NO4 by high resolution FABMS. The IR spectrum displayed absorption bands at 3314 (hydroxyl), 1650, and 1540 cm−1 (amide). The H NMR spectrum showed highly overlapped signals at δ 1.29-1.31, indicative of long aliphatic carbon chain, and the C NMR spectrum suggested the presence of one carbonyl carbon, four carbons attached to heteroatoms, and six olefinic carbons on the basis of their characteristic chemical shifts. All these information of 1 allowed us to deduce a ceramide nature containing three double bonds. This is also supported by the H NMR spectrum measured in pyridine-d5 which showed a downfield proton signal at δ 8.38 (d, J = 8.8 Hz) corresponding to the secondary amide proton (Table 1). The main framework of compound 1 was established by extensive 2D NMR techniques. The methine proton at δ 3.84, connected to a nitrogen-bearing carbon, was coupled to the nonequivalent oxymethylene protons (H-1) at δ 3.66 and

Chemo‐Pharmaceutical Studies on the Glycosphingolipid Constituents from Echinoderm, Sea Cucumbers, as the Medicinal Materials

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Chemo-pharmaceutical studies on the glycosphingolipid constituents from echinoderm, sea cucumbers, as the medicinal materials

Glycosphingolipids (GSLs), together with glycopeptides, are typical constitutents of various cell membranes in a wide variety of organisms. In particular, it is known that GSLs have numerous physiological functions due to variations in the sugar chain, in spite of the very small quantity of constituents. Those are classified into cerebrosides, sulfatides, ceramide oligohexosides, globosides, and gangliosides based on the constituent sugars. Gangliosides, sialic acid-containing GSLs, are especially enriched in the brain and nervous tissues and are involved in the regulation of many cellular events. Recently, a number of GSLs have been isolated from marine invertebrates such as echinoderms, poriferans, and mollusks. We have also been researching biologically active GSLs from echinoderms to elucidate the structure-function relationships of GSLs and to develop novel medicinal resources. This review summarizes the structures and biological activities of GSLs from sea cucumbers. This study showed that the characteristics of GSLs and structure-activity relationships had neuritogenic activity toward the rat pheochromocytoma cell line PC12. That is, most of the cerebroside constituents of the sea cucumber are same glucocerebrosides as in other animals, except for some constituents, while the ganglioside constituents were unique in that a sialic acid directly binds to the glucose of cerebroside, they are mutually connected in tandem, and some are located in the internal parts of the sugar chain. It also became apparent that sialic acid is indispensable for the neuritogenic activities.

Glycosphingolipids of human plasma

A number of glycosphingolipids, including 10 gangliosides, not previously identified in human plasma have been characterized. The plasma contains 2 μg of lipid-bound sialic acid/ml plasma and 54% of the gangliosides are monosialo, 30% disialo, 10% trisialo, and 6% tetrasialo. Individual glycosphingolipids were purified by high-performance liquid chromatography and thin-layer chromatography, and were characterized on the basis of their chromatographic mobility, carbohydrate composition, hydrolysis by glycosidases, methylation analysis, and immunostaining with anti-glycosphingolipid antibodies. The monosialogangliosides were identified as G M3, G M2 sialosyl(2–3)- and sialosyl(2–6)lactoneotetraosylceramides, sialosyllacto- N-nor-hexaosylceramide, and sialosyllacto- N-isooctaosylceramide. The major gangliosides in the polysialo fractions contained a ganglio- N-tetraose backbone and were identified as G D3, G D1a, G D1b, and G Q1b. The most abundant neutral glycosphingolipids were glucosyl, lactosyl, globotriaosyl, globotetraosyl and lactoneotetraosylceramides. The other neutral glycosphingolipids, tentatively identified by immunostaining with monoclonal antibodies, contained H 1, Le a, Le b, and lacto- N-fucopentose III (X hapten) Structures.

Specific cleavage of the glycosidic bond between the carbohydrate and ceramide portions in glycosphingolipids using trifluoroacetolysis.

A number of glycosphingolipids have been subjected to trifluoroacetolysis. Heating the glycosphingolipid at 100 degrees C for 48 h in mixtures of trifluoroacetic acid (TFA) and trifluoroacetic anhydride (TFAA) varying from 1:1 to 1:100 (v/v) resulted in complete cleavage of the glycosidic bond between the carbohydrate and the unsaturated base of the ceramide. The fatty acid(s) linked to the amino group of sphingosine were also released by transamidation. The carbohydrate portion was stable under these conditions due to stabilization of the glycosidic bonds by the electronegative O-trifluoroacetyl groups. The 2-acetamido-2-deoxy-hexose units in the glycosphingolipids were converted into their N-trifluoroacetyl analogues. The N-trifluoroacetyl functions could be removed and the 2-acetamido-2-deoxy-hexoses could be reconstituted by N-acetylation.