RESUMO
The content of sphingolipids in M3 and B16/F10 melanomas with a high metastatic potential and in Claudman's and B16/F1 melanomas with a low metastatic potential was studied. It was shown that the content of total lipid-bound sialic acids and ganglioside GM3 in melanomas with a high metastatic potential is considerably higher than that in melanomas with a low metastatic potential. On the other hand, the ceramide to glucosylceramide molar ratio is higher in melanomas with a low metastatic potential. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.
Assuntos
Melanoma Experimental/metabolismo , Melanoma Experimental/secundário , Esfingolipídeos/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Transplante de NeoplasiasRESUMO
The effects of various bioactive sphingolipids (sphingosine 1-phosphate, sphingosine 1-phosphocholine, ceramide 1-phosphate, ceramide beta-glucoside and beta-lactoside, and gangliosides) on cell proliferation and apoptosis are reviewed. It is concluded that the balance between the bioeffector sphingolipids determines their overall effect on cell. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 3; see also http://www.maik.ru.
Assuntos
Esfingolipídeos/fisiologia , Animais , Ciclo Celular/fisiologia , Proliferação de Células , Sobrevivência Celular/fisiologia , Glicoesfingolipídeos/química , Glicoesfingolipídeos/metabolismo , Glicoesfingolipídeos/fisiologia , Humanos , Fosforilação , Esfingolipídeos/química , Esfingolipídeos/farmacologia , Esfingosina/análogos & derivados , Esfingosina/químicaRESUMO
The content of sphingenine (sphingosine) and sphinganine was determined in the total pool of sphingomyelin and ceramide in the rat tumors transplanted subcutaneously and intrahepatically. The sphingenine/sphinganine ratio in the subcutaneously transplanted sarcoma M1 and cholangiocellular carcinoma RS1 was lower than that in the sphingolipids of the intrahepatically transplanted tumors. However, the sphingenine/sphinganine ratio in the subcutaneously transplanted rat hepatoma 27 was higher than in the intrahepatically transplanted hepatoma. These observations indicate that the sphingenine/sphinganine ratio in sphingolipids of tumors depends on the tumor type and its cellular microenvironment.
Assuntos
Neoplasias Experimentais/metabolismo , Esfingolipídeos/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Animais , Carcinoma/metabolismo , Carcinoma/patologia , Ceramidas/química , Ceramidas/metabolismo , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Experimentais/patologia , Especificidade de Órgãos , Ratos , Sarcoma Experimental/metabolismo , Sarcoma Experimental/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Esfingolipídeos/química , Esfingomielinas/química , Esfingomielinas/metabolismo , Esfingosina/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The bioregulatory functions of sphingolipids devoid of 4E-double bond in the sphingoid chain are discussed; the sphingolipids are shown to be biologically active. The English version of the paper.
Assuntos
Esfingolipídeos/química , Esfingolipídeos/fisiologia , Esfingosina/análogos & derivados , Animais , Ceramidas/química , Ceramidas/metabolismo , Humanos , Fosforilcolina/metabolismo , Esfingosina/química , Esfingosina/metabolismo , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Esfingolipídeos/química , Esfingolipídeos/metabolismo , Animais , Humanos , Relação Estrutura-AtividadeRESUMO
Activity of neutral and acidic sphingomyelinases (N- and A-SMases) were studied in regenerating liver after partial hepatectomy (during 48 hrs after operation), in ischemic liver during 15, 30 min and 1 and 2 hrs ischemia and during following reperfusion (from 5 min up to 2 hrs), in hepatoma- 22 after 15 days of transplantation and in liver of tumor bearing animals. It was shown that activity of N-SMase is increased in hepatoma-22 and in regenerating liver and it is decreased in ischemic liver. Following reperfusion of ischemic liver area activity of enzyme was found to have returned to baseline in dependence on time of ischemia and reperfusion. Activity of A-SMase is decreased in tumor, is not changed in regenerating liver and increased after long time of ischemia. It was supposed that N-SMase is involved in cell proliferation, but A-SMase is connected with cell damage.
Assuntos
Neoplasias Hepáticas Experimentais/enzimologia , Regeneração Hepática , Fígado/irrigação sanguínea , Fígado/enzimologia , Esfingomielina Fosfodiesterase/metabolismo , Animais , Feminino , Isquemia/enzimologia , Isoenzimas/metabolismo , Camundongos , Ratos , Ratos WistarRESUMO
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.
Assuntos
Neoplasias/metabolismo , Esfingolipídeos/metabolismo , Transformação Celular Neoplásica , Análise de Alimentos , Humanos , Neoplasias/terapia , Esfingolipídeos/química , Esfingolipídeos/uso terapêuticoRESUMO
Composition and content of ceramides and gangliosides from different kinds of human ovary benign and malignant epithelial tumours were studied. The ceramide content was shown to decrease significantly in the tumours, especially in malignant tumours, in comparison with the normal ovary tissue. In the tumour ceramides a sphingosine base composition changes: sphinganine was found along with sphingenine, which is characteristic for normal ceramides. The fatty acid composition changes also. Main tumour gangliosides were shown to be GM3 and GD3. Their content decreases in malignant ovary tumours, especially the amount of ganglioside GD3. As a result of these changes the molar ratio Cer/Sia decreases. It can appears stimulates a tumour growth.
Assuntos
Ceramidas/análise , Gangliosídeos/análise , Cistos Ovarianos/química , Neoplasias Ovarianas/química , Ovário/química , Feminino , Humanos , Cistos Ovarianos/patologia , Neoplasias Ovarianas/patologiaRESUMO
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.
Assuntos
Envelhecimento/metabolismo , Ceramidas/metabolismo , Gangliosídeos/metabolismo , Ovário/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Transformação Celular Neoplásica , Esfingolipídeos/metabolismo , Membrana Celular/metabolismo , Neoplasias/tratamento farmacológico , Esfingolipídeos/uso terapêuticoRESUMO
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.
Assuntos
Ácido Araquidônico/metabolismo , Gangliosídeo G(M3)/fisiologia , Lipoxigenase/metabolismo , Baço/metabolismo , Animais , Células Cultivadas , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos CBA , Oxirredução , Baço/citologiaRESUMO
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.
Assuntos
Amidas/química , Gangliosídeos/química , Amônia/química , Sequência de Carboidratos , Cromatografia em Camada Fina , Humanos , Dados de Sequência MolecularRESUMO
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.
Assuntos
Neoplasias da Mama/química , Gangliosídeo G(M3)/análise , Gangliosídeos/análise , Lactonas/análise , Neoplasias Gástricas/química , HumanosRESUMO
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.
Assuntos
Anticorpos/imunologia , Gangliosídeos/sangue , Animais , Sequência de Carboidratos , Gangliosídeos/imunologia , Humanos , Dados de Sequência MolecularRESUMO
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.
Assuntos
Gangliosídeos/metabolismo , Linfonodos/química , Linfoma de Células T/química , Animais , Cromatografia Líquida , Cromatografia em Camada Fina , Gangliosídeos/sangue , Papio , Valores de ReferênciaRESUMO
Gangliosides were studied in blood serum of healthy volunteers and of patients with cancer of mammary gland and stomach. Blood serum of the majority of patients with cancer and only 15% of healthy persons were shown to contain ganglioside GD3 which was detected in blood of patients with some other tumors.
Assuntos
Neoplasias da Mama/sangue , Gangliosídeos/sangue , Neoplasias Gástricas/sangue , Cromatografia em Camada Fina , Humanos , Valores de ReferênciaRESUMO
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.
Assuntos
Neoplasias da Mama/química , Gangliosídeo G(M3)/análise , Gangliosídeos/análise , Neoplasias Gástricas/química , Gangliosídeo G(M1)/análise , HumanosRESUMO
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.
Assuntos
Gangliosídeos/metabolismo , Lipoxigenase/metabolismo , Linfócitos/enzimologia , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico , Ácido Araquidônico , Ácidos Araquidônicos/metabolismo , Cromatografia Líquida de Alta Pressão , Humanos , Ácidos Hidroxieicosatetraenoicos/biossíntese , Células Matadoras Naturais/imunologia , Oxirredução , Espectrofotometria UltravioletaRESUMO
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.