Biomedical subjects
Publications and source records attributed to E V Diatlovitskaia.
The interrelation between the bioeffector functions of sphingolipids and their chemical structure is reviewed. The effects of modifications of sphingoid functional groups on the bioregulatory properties of sphingolipids in cell proliferation, differentiation, and apoptosis are discussed.
The qualitative and quantitative changes in sphingolipids (ceramides, sphingomyelins, glycosphingolipids) occurring under tumor growth are considered. The influence of these changes on cell functions and immunity as well as the role of dietary sphingolipids in cancer and "sphingolipid" therapy of tumors are discussed.
The age dependence of the ceramide and ganglioside content in human ovaries has been studied. It has been found that the ganglioside content does not change upon ageing, while the ceramide content alters with age, showing initial increase around the age of 45-47 years but then drops drastically. The composition of gangliosides undergoes drastic changes in the course of time, GM3 and GD3 being the major gangliosides in human ovaries. The amount of GD3 increases with age with a subsequent reduction of the Cer/GD3 molar ratio. It is suggested that the reduction of the Cer/GD3 molar ratio is a "risk factor" in tumour development upon ageing.
Data concerning qualitative and quantitative changes in sphingolipids (ceramides, sphingomyelins, glycolipids) occurring under cell malignization are reviewed. The influence of these changes on biological functions of cell membranes and immunity as well as "sphingolipid" therapy of tumours are discussed.
The main arachidonic acid metabolites released into the medium by mouse splenocytes have been identified on the basis of chromatographic and spectral studies as well as by mass spectrometry of the derivatives. In the absence or presence of exogenous arachidonic acid mouse splenocytes produce mainly 12-hydroxy-5,8,10,14-eicosatetraenoic and 12,20-dihydroxy-5,8,10,14-eicosatetraenoic acids. Both products are constantly released by intact cells into surrounding media without stimulation by exogenous substrate or other modulators. For the first time it is shown that exogenously added ganglioside GM3 lactone as well as ganglioside GM3 itself can influence the arachidonic acid metabolism in splenocytes.
Ganglioside lactones absent in homologous normal tissues have been found in minute amounts in human gastric and mammary tumours. In mammary gland tumours only the ganglioside GM3 lactone has been identified. Gastric tumours also contain the GM3 lactone; in one case a ganglioside GD3 lactone was identified.
Analysis of natural ganglioside lactones usually employs NH3 treatment. In the present paper it has been shown that the GD3 dilactone forms with ammonia three rather than one GD3 amides--a GD3 diamide and two GD3 monoamides. The structure of these amides is discussed.
The concentration and composition of gangliosides from normal and pathological blood serum of animals and man are reviewed. Data concerning the elevation of the ganglioside content in the serum under malignization are summarized. The appearance of ganglioside-specific antibodies in some pathological states is described. The possible influence of changes in the serum ganglioside content and composition on immunity is discussed.
Gangliosides of human gastric and mammary tumours and of homologous normal tissues were studied by using biochemical methods and specific antisera. It was found that in most cases GM3, GD3 and GM1 are predominant gangliosides, whereas several polar components are minor ones. A comparison of the relative amount of ganglioside fractions revealed that in gastric tumours the per cent content of polar compounds is higher than in intact tissue; however, the absolute content of all gangliosides is markedly increased. A comparative study of the composition of mammary tumour and normal tissue gangliosides demonstrated two types of changes: i) the absolute content of all gangliosides in tumour tissue was increased and, ii) the increase in the content of total gangliosides was paralleled with the appearance of a new fraction (presumably GM4), the decrease of the GD3 content and the disappearance of polar gangliosides. A possible mechanism of this effect is discussed.
Using reverse phase high performance chromatography with UV-detection, the arachidonic acid cascade in human peripheral blood lymphocytes (PBL) was studied. It was found that PBL oxidized arachidonic acid via the lipoxygenase pathway, 12-hydroxyeicosatetraenoic acid (12-HETE) being the major metabolite of endogenous arachidonic acid. Exogenous arachidonic acid added to human PBL suspensions increased 12-HETE synthesis 5-7 times. In another experimental series the effects of gangliosides (GD3, GM1 and GM3) on lipoxygenase-catalyzed oxidation of arachidonic acid in human lymphocytes were investigated. All the gangliosides tested stimulated PBL to secrete 12-HETE both from endogenous and exogenous arachidonic acid. In most cases the stimulating effect of GD3 was much more apparent that those of GM1 and GM3.
The gangliosides from the lymph nodes and blood sera of normal and T-lymphomic baboons were studied. In lymph nodes the major gangliosides were identified as GM3 and GD3, those in blood sera--as GM3, GM1 and GD3. Gangliosides GM3 and GD3 contained N-acetyl as well as N-glycoloyl neuraminic acids. In gangliosides isolated from lymph nodes and blood sera of T-lymphomic baboons the levels of N-glycoloyl neuraminic acid markedly exceeded that in normal tissues. In tumour lymph nodes the GM3/GD3 ratio was shifted towards GD3.
The derivatives of ganglioside GM3-NeuLacCer. NeuLacSph and NeuAcLacSphAc-were obtained and their immunomodulating properties studied. These substances are shown to inhibit lymphocyte blast-transformation independently of their ceramide structure. On the contrary, the stimulation by the above GM3-derivatives of Con A-induced T-suppressor activity depends significantly on the structure of their ceramide moiety.
The fatty acids and sphingosine bases from major placenta gangliosides (NeuAcLacCer, IV3NeuAc-nLc4Cer, VI3NeuAc-nLc6Cer, (NeuAc)2LacCer, II3IV3(NeuAc)2Gg4Cer and VI3NeuAc, IV6(II3NeuAc-nLcNAc)-nLc6Cer) were studied. The C18-sphingenine was shown to be present in all ganglioside fractions; fraction GD1a contained, in addition, C20-sphingenine. Saturated fatty acids were identified as major fatty acid fragments. The content of long-chain acids (22-25 C-atoms) in the monosialogangliosides was much higher than that in disialogangliosides.
Gangliosides NeuAc-LacCer, NeuGc-LacCer, NeuLac-Sph and NeuAc-LacSphAc were analysed by FAB mass spectrometry in the negative ion mode. It is shown that this method gives valuable information on the structure of carbohydrate chains and fatty acid residues of the ganglioside molecules taking only micrograms of substances.
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Glycosphingolipids are immunogenic components of cell surface whose composition and structure change during the cell transformation. The contemporary state of the question about the influence of glycosphingolipids on specific and non-specific antitumour immunity is considered. The available information about shedding of glycosphingolipids from the tumour cell surface, about the change of the ganglioside content in blood serum of the tumour host and about the effect of glycolipids on immunocompetent cells is analyzed. The results obtained by the authors in studies of the influence of glycosphingolipids on effector cells of the body natural resistance system to tumour are discussed.