Sphingolipid receptors.

The role of sphingolipids as receptors of bacteria, viruses, and toxins and also as ligands of proteinaceous receptors involved in the cell-cell signaling in animals is considered.

The role of lysosphingolipids in the regulation of biological processes.

This review summarizes data on the role of lysosphingolipids (glucosyl- and galactosylsphingosines, sphingosine-1-phosphate, sphingosine-1-phosphocholine) in the regulation of various biological processes in normal and pathological states.

Sphingolipids in tumor metastases and angiogenesis.

This review article summarizes data on the involvement of sphingolipids (sphingosine-1-phosphate, sphingosine-1-phosphocholine, neutral glycosphingolipids, and gangliosides) in tumor metastases and angiogenesis.

Role of biologically active sphingolipids in tumor growth.

This review highlights the literature on the effects of biologically active sphingolipids (sphingosine, ceramide, sphingomyelin, glucosylceramide, gangliosides GM1, GM2, GM3, GD3, etc.) on proliferation, apoptosis, metastases, and invasiveness of tumor cells and the putative role of sphingolipids in chemotherapy of malignant tumors.

Change in contents of biologically active sphingolipids modulating cell growth and survival in hepatoma 27 compared to rat liver.

The contents of bioactive sphingolipids (sphingomyelin, ceramide, glucosyl- and lactosylceramides, gangliosides) were studied in rat hepatoma 27 and rat liver. The amounts of sphingomyelin, ceramide, and glucosyl- and lactosylceramides were about twofold and that of gangliosides was about 3.5-fold increased in the tumor compared to normal tissue.

Comparative study of lipid composition and proliferative activity of rat cholangiocarcinoma RS1 and sarcoma M1 depending on the transplantation organ.

The proliferative activity and lipid composition (phospholipids, gangliosides) were studied in rat cholangiocarcinoma RS1 and sarcoma M1 transplanted subcutaneously or intrahepatically. The mitotic index was higher in the tumors transplanted into the heterologous organ. The total phospholipid and sphingomyelin contents were higher in the tumors transplanted intrahepatically.

Dihydroceramide desaturase activity in tumors.

Dihydroceramide desaturase activity in the transplantable mouse hepatoma-22, rat hepatoma-27, M1 sarcoma, and RS1 rat cholangiocellular carcinoma has been investigated. It was found that the dihydroceramide desaturase activity in mouse hepatoma-22 is lower than that in normal mouse liver. However, the activity of this enzyme in subcutaneously and intrahepatically transplanted rat hepatoma-27 is increased compared to normal value.

Differences in lipid composition and proliferative activity of rat hepatoma-27 depending on the target organ.

Proliferative activity and lipid composition (phospholipids and gangliosides) were studied in rat hepatoma-27 transplanted subcutaneously or intrahepatically (as models for primary and metastasizing tumors). The mitotic index of subcutaneously transplanted hepatoma far exceeded that of the intrahepatically transplanted tumor. The overall amounts of both phospholipids and gangliosides increased appreciably in the subcutaneously growing hepatoma (in contrast to the intrahepatically growing tumor) in comparison to the control hepatic tissue.

Sphinganine in sphingomyelins of tumors and mouse regenerating liver.

Contents of sphingenine (sphingosine) and sphinganine were studied in sphingomyelins of transplantable mouse tumors (hepatoma-22, melanoma B16, Lewis lung carcinoma, intestine carcinoma) and rat nephroma RA. The content of sphinganine was increased in sphingomyelins of hepatoma-22 and nephroma RA compared to sphingomyelins of liver and kidneys. Significant contents of sphinganine were also found in sphingomyelins of other studied tumors.

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.

Content and structure of ceramide and sphingomyelin and sphingomyelinase activity in mouse hepatoma-22.

The relative content of phosphatidylcholine is lower and that of sphingomyelin is higher in transplantable fast growing mouse hepatoma-22, thus decreasing their ratio approximately 2.5-fold versus normal liver. The ceramide content and the neutral sphingomyelinase activity is markedly higher (3- and 6.

Comparative investigation of sphingoid bases and fatty acids in ceramides and sphingomyelins from human ovarian malignant tumors and normal ovary.

Fatty acid and sphingoid base compositions of ceramides and sphingomyelins were investigated in malignant tumors and normal tissue of human ovaries. It has been established that fatty acid compositions of ceramide and sphingomyelin isolated from one tissue are significantly different: the predominant acids are oleic (18:1) in ceramide and palmitic (16:0) in sphingomyelin, which contains much more other saturated acids. These differences are characteristic of both normal and tumor tissues.

Correlation between bioeffector characteristics of sphingolipids and the structure of their hydrophobic fragment.

The effect of the structure of the hydrocarbon sphingoid base chain (length, presence of double bonds, and steric configuration of functional groups) and the length of the fatty acid residue of a ceramide molecule on the bioregulatory activities of sphingoids and ceramides is reviewed. Particular emphasis is placed on the role of functional groups (OH- and NH2-) typical of the sphingoid chain.

Antiproliferative activity of ceramides isolated from normal human ovary and ovarian tumor.

Ceramides modulate cell growth, differentiation and apoptosis. We have previously demonstrated that human epithelial ovarian tumors contain dihydroceramides that are absent from normal ovary. Dihydroceramides differ in their biological effects from ceramides; therefore antiproliferative activity of ceramides isolated from normal human ovary and ovarian tumors was studied.

Nanomolar concentrations of gangliosides stimulate primary humoral response.

Exogenous gangliosides act as immunosuppressors when applied at micromolar concentrations corresponding to their average level in human plasma. Here we show that at nanomolar concentrations the gangliosides GD3, GD1a and GM1 can act as immunostimulators markedly enhancing the number of plaque-forming cells in mouse splenocyte culture responding to sheep erythrocytes. At such low concentration these gangliosides as well as GM3 were not able to influence significantly proliferative responses of splenic B and T lymphocytes or of cytotoxic T-cells.

Ganglioside shedding and changes in ceramide biosynthesis in human ovarian tumors.

The contents and composition of ceramides and gangliosides were measured in human ovarian tumors (benign and malignant) and sera of tumor patients. In tumors (especially malignant) the content of ceramides is decreased compared to that in normal tissue, and the malignant tumor ceramides contain significant amounts of sphinganine which is absent in the ceramides of normal tissue, suggesting an alteration in ceramide biosynthesis. The content of gangliosides in tumors is also decreased.

Influence of ganglioside GM3 and its breakdown products on lymphoblastic transformation and T-suppressor activity.

The influence of ganglioside GM3 and some of its breakdown products on phytohemagglutinin-induced blast transformation of human lymphocytes and concanavalin-A-induced T-suppressor activity was studied. The structures of two major hydrolysis products of GM3 were established by negative-ion fast-atom-bombardment mass spectrometry as neuraminyllactosylsphingosine (NeuLacSph) and neuraminyllactosylceramide (NeuLacCer). Both substances were shown to be potent inhibitors of mitogen-induced lymphoblastic transformation whereas their acetylation products NeuAcLacSphAc and GM3 did not affect the proliferative response of lymphocytes to phytohemagglutinin.

Immunomodulatory effects of human placenta gangliosides.

The immunomodulatory properties of the major gangliosides of human placenta were studied. All the gangliosides investigated suppressed the cytotoxic activity of human natural killer cells. The magnitude of the inhibitory effect depended on ganglioside structure.

The role of glycosphingolipids in natural immunity. Gangliosides modulate the cytotoxicity of natural killer cells.

Incubation of gangliosides with natural killer (NK) cells from various sources was found to inhibit NK activity in vitro whereas incubation of the same gangliosides with human or mouse lymphoma cells prior to their exposure to NK effectors resulted in a sharp increase in the NK sensitivity of the tumor cells. These effects depended on the oligosaccharide structure of the gangliosides and on the origin of the NK effector cells. The lysis of YAC cells by mouse splenocytes or of MOLT-4 cells by NK cells isolated from the peripheral blood of Syrian hamsters or humans was inhibited most strongly by pre-incubation of the effector cells with gangliosides GM3 and GD3 which are known to be elevated in the serum of tumor-bearing hosts.

Shedding of gangliosides from calf thymocytes.

In the course of our work on calf thymus gangliosides [Dyatlovitskaya, Zablotskaya, Azizov & Bergelson (1980) Eur. J. Biochem.

A sphingomyelin transfer protein in rat tumors and fetal liver.

The binding of the disaccharides methyl beta-D-lactoside and 2-acetamido-2-deoxy-3-O-(beta-D-galactopyranosyl)-beta-D-galactopyranose [beta-D-Gal-(l leads to 3)-D-GalNAc] to peanut agglutinin was studied by ultraviolet difference spectroscopy. The magnitude of the difference spectra varied with the concentration of the carbohydrates; association constants and thermodynamic parameters were determined from titration experiments at different temperatures. The enthalpy and entropy changes for binding of methyl beta-D-lactoside were found to be delta H degree = -65 +/- 4 kJ mol-1, delta S degree = -156 +/- 14 J mol-1 K-1.

Gangliosides of calf thymus and of normal and leukemic bovine lymphocytes.

The gangliosides of calf thymus and of lymphocytes from blood, lymph nodes, lymph and spleen of normal and leukemic cows were investigated in an attempt to determine whether there exists a relation between the ganglioside composition and the maturity of the lymphocytes. With all normal peripheral lymphocytes studied the largely prevailing (up to 97%) ganglioside component was found to be N-glycoloylneuraminosyllactosylceramide. The ganglioside spectrum of calf thymus was much more complex and included at least six different components.

Use of protein-mediated lipid exchange in the study of membrane-bound enzymes. The lipid dependence of glucose-6-phosphatase.

The ability of liver lipid-exchange proteins to introduce foreign phospholipids into microsomes was used in a study of the lipid dependence of glucose-6-phosphatase. Supplementation of intact rat liver and hepatoma microsomes with exogeneous aminophospholipids prevents the decline of glucose-6-phosphatase activity during incubation, whereas the introduction of exogeneous phosphatidylcholine has no protective effect. On the contrary with deoxycholate-disrupted hepatoma microsomes, introduction of additional phosphatidylcholine causes activation while phosphatidylethanolamine has only little effect.