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A V Alesenko

Publications and source records attributed to A V Alesenko.

At least 19 recordsLinked to original sources
PubMed2005

[The influence of tumor necrosis factor alpha on the processes of sphingomyelin cycle and lipid peroxidation in brain].

The influence of tumor necrosis factor alpha (TNF-alpha) on the processes of sphingomyelin cycle activation and intensity of peroxidation in animal brain in vivo has been studied. Alterations in activity of sphingomyelinase, a key sphingomyelin cycle enzyme and in sphingomyelin, ceramide content as well as accumulation of the products of lipid peroxidation (diene conjugates and diene ketons) were measured in the cortex, the cerebellum and the hippocampus of rats 5, 15, 30 min, 1, 2 and 5 hours after TNF-alpha intraperitoneal injection in dosage 100 mkg per animal. It is shown that 2 hours after the injection, TNF-alpha initiated an accumulation of the products of lipid peroxidation, which intensively developed in the cerebellum and the hippocampus. Sphingomyelinase activation was found in the same brain structures. At the initial stage of TNF-alpha action, an increase of lipid peroxidation products correlated with sphingomyelinase activation in the cerebellum and the hippocampus suggesting an interaction of two cell signal systems of sphingomyelin cycle and oxidative system.

Animals↗
PubMed1999

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 6.5-fold, respectively), whereas the acid sphingomyelinase activity is 4-fold lower in hepatoma-22 versus normal liver. The content of saturated fatty acids in ceramide and sphingomyelin of hepatoma-22 is higher than in normal liver. All sphingolipids of hepatoma-22 contain a considerable amount (25-37%) of sphinganine (dihydrosphingosine) along with sphingenine (sphingosine), whereas sphingolipids of normal liver contain predominantly sphingenine (over 95%). These results indicate that the activity of enzymes involved in sphingolipid biosynthesis and catabolism is disturbed in the transplantable mouse hepatoma-22 compared to normal liver.

Animals↗
PubMed1998

TNF alpha-induced aerobic synthesis of ATP on plasma membranes of target cells. The relation to the expression of the nuclear oncogene c-myc.

The accumulation of ATP by preparations of plasma membranes enriched particles (PMEP) isolated from rat hepatocytes, murine splenocytes and human T-lymphocytes has been investigated after the binding of human and murine tumour necrosis factors (TNF alpha) to their specific receptors. The TNF alpha-induced expression of the nuclear oncogene c-myc in intact hepatocytes has been also studied. TNF alpha induced the marked biosynthesis of ATP on PMEP of hepatocytes and splenocytes within the first minute of incubation. The biosynthesis of ATP was independent of the activity of adenylate kinase and only occurred in the presence of all the components of aerobic phosphorylation and the electron acceptor, cytochrome C or diferric transferrin. The level of ATP on PM correlated with the degree of expression of the nuclear oncogene c-myc in the same target cells. Adriamycin totally suppressed the biosynthesis of ATP on PM and simultaneously inhibited the expression of c-myc. The ATP synthesized on PM is suggested to be involved in transduction of the proliferative or growth signal to the cell nucleus.

Adenosine Triphosphate↗
PubMed1995

[Correlation of cytotoxic activity of mutant forms of tumor necrosis factor alpha with changes in the level of free sphingosine in murine liver].

Sphingosine, the product of enzymatic degradation of sphingomyelin, displays a high cytotoxic activity and is accumulated in animal organs under the action of the tumour necrosis factor (TNF alpha). To elucidate the role of sphingosine in the realization of TNF cytotoxicity, TNF mutants were obtained which differed in their cytotoxic action on L929 cells. The wild strain of TNF and the mutant having a deletion in position 67-71 displayed the highest toxicity and sharply stimulated sphingosine accumulation in mouse hepatocytes. A moderate increase in the sphingosine content was induced by mutants with point and double mutations in positions E127Q, I155L and V150I displaying a much lower toxicity in comparison with the wild strain. The toxic, mutagenic and antimutagenic activities of sphingosine were investigated. Despite the high degree of cytotoxicity, sphingosine did not display any mutagenic activity but had a pronounced antimutagenic effect on E. coli cells. The role of phospholipid enzymatic degradation products in activation of sphingomyelin cycle enzymes stimulating of sphingosine accumulation in animal cells under the action of TNF alpha is discussed.

Amino Acid Sequence↗
PubMed1995

[Modulation of the level of sphingomyelin cycle products and expression of the CD3 receptor in immunocompetent organs by fumonisin B1].

The fungi (Fusarium moniliforme) residing on cereals produce a broad range of mycotoxins, among which fumonisins display a high toxicity alongside with carcinogenic and teratogenic activities. Taking into account the ability of fumonisins to inhibit sphingolipid synthesis, the role of sphingomyelin cycle products in immune reactions was studied with the view of establishing the correlation between the expression of the surface receptor CD3 in immunocompetent organs (spleen, thymus) (T-cell mediated immunity) and the degree of sphingomyelin cycle activation (changes in the activities of sphingomyelinase and sphingomyelin and ceramide content) in the spleen, thymus and liver 2.5 hours after intraperitoneal injection of fumonisin B1 (FB1) (5 and 20 micrograms/animal). Significant sphingomyelinase activation was found in the thymus of animals injected with 20 micrograms of fumonisin. It coincides with a loss of the sphingomyelin and ceramide content. The changes in the sphingomyelinase activity and sphingomyelin content in the spleen and in the liver caused by fumonisin were insignificant, while the ceramide content dropped drastically. Fumonisin decreased the receptor CD3 expression on the surface of thymus cells "in vitro" and "in vivo", which is consistent with the sharp decrease of the ceramide content in this organ. Ceramide accumulation in thymus and spleen cells treated with sphingomyelinase in vitro correlates with the increased affinity of receptor CD3. The putative role of ceramide in the expression of receptors modulating T-cell mediated immunity under the influence of fumonisin is discussed.

Animals↗
PubMed1994

[Correlation of DNA degradation, induced by tumor necrosis factor-alpha, with accumulation of sphingosine in the nucleus and peroxides in DNA].

The tumour necrosis factor alpha (TNF-alpha) initiates DNA degradation in many types of cells, eventually resulting in a programmed cell death (apoptosis). In order to study the mechanism of TNF-alpha action in vivo, the dynamics of mouse liver DNA fragmentation was examined after intraperitoneal administration of recombinant hTNF-alpha (10 and 40 micrograms per animal). The number of single-strand (SSB) and double-strand (DSB) breaks was determined electrophoretically and interruption of hydrogen bonds (secondary structure defects SSD) were studied by the kinetic formaldehyde method. In parallel experiments the accumulation of peroxide products in DNA, the activity of sphingomyelinase and the content of sphingosine in liver cell nuclei were measured. Sphingomyelinase activation and sphingosine accumulation in the nuclei were found to coincide in time with the maximal values of DNA degradation parameters (SSB, DBS and SSD). TNF-alpha caused a dose-dependent accumulation in DNA peroxide products which seem to lead to the DNA damages. The role of sphingomyelin cycle products and peroxidation in DNA fragmentation induced by TNF-alpha in vivo is discussed.

Animals↗
PubMed1994

[Change in the level of sphingosine in rat liver nuclei and cells during oncogene superexpression induced by cycloheximide].

Changes in the sphingosine content in rat liver cells and nuclei have been studied with reference to the level of nuclear oncogene expression, induced by cycloheximide (0.1, 0.5 and 3.0 mg/kg). It has been found that only the sublethal (3 mg/kg) dose of cycloheximide which induces the superexpression of c-fos and c-myc oncogenes can promote sphingosine accumulation in the cell. At the moment of enhanced expression of nuclear oncogenes, the maximum content of free sphingosine exceeds the control level 1.5- and 3-fold in the cell and in the nuclei, respectively. The difference in the sphingosine accumulation patterns in the cell and in the nuclei testifies to the fact that sphingomyelin metabolism is more active in the nuclei than in the cell. Sphingosine accumulation in the nuclei is characterized by coordination of sphingomyelinase activity and changes in the sphingomyelin content. A comparative analysis of activities of enzymes of sphingomyelin (sphingomyelinase) and phosphatidyl inositol (phosphatidyl inositol kinase) cycles indicates that in the nuclei the activation of the sphingomyelin cycle forestalls the cycloheximide-induced activation of the phosphatidyl inositol cycle and the maximal accumulation of nuclear oncogene mRNAs. A model of activation of oncogene expression with participation of sphingosine inhibiting protein kinase C and activating casein kinase II, the key enzymes of the signal transduction system of cell proliferation and differentiation, is proposed.

Animals↗
PubMed1993

[Change in the level of endogenous sphingosine in cell nuclei from regenerating rat liver].

High-performance liquid chromatography was used to study the changes in the sphingosine content in regenerating rat liver cell nuclei during RNA and DNA synthesis. It was found that activation of nucleic acid synthesis was accompanied by sphingosine accumulation in cell nuclei in parallel with the induction of the sphingomyelin cycle consisting in the increasing activity of sphingomyelinase and alteration of the sphingomyelin and ceramide content. To clarify the mechanism of sphingosine involvement in replication and transcription, the ability of this product to interact with DNA and modify the activity of RNA-polymerase in vitro was studied. At 10(-4) M sphingosine prevented the interaction of acridine orange with DNA and activated the transcription enzymes. Several alternative mechanisms of sphingosine involvement in the control of nucleic acid synthesis are discussed.

Animals↗
PubMed1993

[The effect of tumor necrosis factor on the free sphingosine level and sphingomyelinase in murine liver cells and nuclei].

The effects of the human recombinant tumour necrosis factor (TNF) (10 and 40 mg/kg of body mass) on sphingomyelinase activity and sphingosine content in mouse (C57bl) liver cells and nuclei have been studied. Whereas sphingomyelinase is known to be a key enzyme of sphingomyelin metabolism, sphingosine, being a product of deep enzymatic hydrolysis of sphingomyelin, controls the activity of various phosphokinases. The primary response of liver cell to TNF consists in the inhibition of sphingomyelinase; its activation occurs at later periods: after 2 hours at 10 mg/kg TNF and after 4 hours at 40 mg/kg TNF. In the nucleus activation of sphingomyelinase is observed within the first 60 min after TNF administration. Sphingosine accumulation in mouse liver cells and nuclei coincides in time with sphingomyelinase stimulation. In the nuclei activation of the sphingomyelin cycle by TNF is far more pronounced than in the cells, being observed at early periods after TNF injection. A signal mechanism of TNF action on mouse liver cells and nuclei involving a TNF-specific receptor and sphingosine which may activate this receptor phosphorylation is discussed.

Animals↗
PubMed1991

[Comparison of lipid metabolism in rat liver cells and nuclei during cycloheximide-induced superinduction of nuclear oncogenes].

Using a model of cycloheximide (CHI)-induced expression of nuclear oncogens, a comparative study of metabolism of the major lipid classes in rat liver nuclei and cells was carried out. A short-term activation of sphingomyelinase which preceded on a time scale the maximal accumulation of c-fos and c-myc transcripts was observed both in the cells and in the nuclei. In contrast with the whole cell, the level of phospholipase C activity in the nuclei did not change under conditions of oncogene activation. It was found that the maximal expression of nuclear oncogens coincided in time with cyclic changes in the content of practically all phospholipids and neutral lipids with simultaneous activation of their synthesis both in the cells and in the nuclei. However, in the nuclei the sphingomyelin metabolism activation was predominant. It is concluded that in the nucleus sphingomyelin and its metabolites may influence oncogene expression via nuclear protein kinase C.

Animals↗
PubMed1991

[Study of sphingomyelinase activity and sphingomyelin and ceramide levels in comparison with other lipid fractions of the cell nucleus in regenerating rat liver].

The changes in the activity of cell nuclear sphingomyelinase at different times of activation of RNA and DNA syntheses in regenerating rat liver were studied. A comparative analysis of the intranuclear content of sphingomyelin and the primary product of the sphingomyelinase reaction, ceramide, as well as of other classes of phospholipids and neutral lipids, was carried out. The changes in the sphingomyelin and ceramide content in the nuclei during the induction of synthetic processes were more conspicuous as compared with other phospholipid classes. Neutral lipids of cell nuclei were also shown to undergo substantial changes. The mechanism of possible involvement of sphingomyelin and other lipids in the regulation of replication and transcription processes is discussed.

Animals↗
PubMed1991

[Effect of sphingomyelin and its enzymatic hydrolysis products on heterologous methylation of calf thymus DNA by cytosine-DNA-methyltransferase EcoRII].

It was found that sphingomyelin and its enzymatic hydrolysis products, choline and sphingosine, influence the degree of DNA methylation in the reaction of heterologous methylation by methylase EcoRII in vitro. Sphingomyelin was found to be able to was activate (by 20%), sphingosine and choline inhibit methylation. Phosphatidylcholine had no effect on DNA methylation in an in vitro system. The role of lipids in the regulation of gene expression during enzymatic modification (methylation) of DNA is discussed.

Animals↗
PubMed1989

[Effect of cycloheximide on lipid metabolism in cells, nuclei and subcellular fractions in the rat liver].

Well coordinated stages of inhibition, restoration and stimulation of protein, DNA and RNA synthesis were observed after administration of cycloheximide (3 mg/kg). The changes in lipid synthesis and composition in the nuclei and intranuclear structures were studied at different stages of cycloheximide action. The accumulation and stimulation of lipid synthesis in the nuclei during the inhibition and restoration of protein and DNA syntheses were followed by electron microscopy and labeled precursors methods. Dramatic changes were observed in the phospholipid composition of chromatin and nuclear matrix. The accumulation of minor phospholipid fractions in intranuclear structures was observed during DNA synthesis. The sphingomyelin concentration was predominant and commensurable with those of phosphatidylcholine and phosphatidylethanolamine.

Animals↗
PubMed1989

[A comparative evaluation of the level of sphingomyelinase activity in liver cell nuclei and in the brain].

It was discovered that there is sphingomyelinase activity in the rat liver nuclei. The maximum of enzyme activity is at pH 7.1. The data obtained demonstrated that the main part of sphingomyelinase is located in the nuclear membrane. Comparison of sphingomyelinase activity in cell nuclei, liver and brain homogenates shows high level of enzyme activity in the nuclei. The authors discuss possible participation of sphingomyelinases in changes of phospholipids composition in nuclear structure under different functional activity of cell nuclei.

Animals↗
PubMed1984

[Sequential activation of various types of nuclear RNA polymerases of rat liver cells during the process of DNA synthesis induction by cycloheximide].

The dynamics of changes in the activity of RNA polymerases I and II (EC 2.7.7.6) and the activities of free and bound forms of RNA polymerase II in isolated rat liver nuclei after a singular injection of sublethal dose of cycloheximide (CHI) was studied. Activation of RNA polymerases occurs in three steps. The first step (1--2 hours after CHI injection) coincides with inhibition of protein synthesis and predominant activation of both forms of RNA polymerase II. The second step (6--24 hours after CHI injection) is characterized by de novo protein synthesis and activation of RNA polymerase I and RNA polymerase II. The third step (36--48 hours after CHI injection) witnesses activation of both RNA polymerases which coincides with the beginning of stimulation of DNA replication. It is assumed that this step is coupled with the synthesis of a special form of RNA polymerase, RNA polymerase IV, which is responsible for transcription of genes synthesizing various chromatin components (histones, NHB, RNA prime). At all steps the activity of free RNA polymerase II remains at a sufficiently high level. Consequently, the activity of chromatin is limited by chromatin structure rather than by RNA polymerase II content in it. Presumably, such activation of various forms of RNA polymerase is essential for cell preparation for DNA replication.

Animals↗
PubMed1984

[Effect of sphingomyelin on RNA-polymerase activity in the cell nucleus of normal and regenerating rat liver].

Using a model of regenerating rat liver, it was shown that the activities of RNA polymerases I and II, and the ratio of free to template engaged form of the enzyme are correlated with the changes in the contents of sphingomyelin in chromatin isolated from cell nuclei of hepatectomized animals. Injections of sphingomyelin to intact and hepatectomized animals in doses increasing its contents in chromatin, stimulate the activity of RNA polymerases I and II and increase the ratio of free to engaged form of the enzyme. Addition of sphingomyelin as a micellar suspension to heterochromatin in vitro facilitates RNA polymerase binding to the template. Removal of sphingomyelin from the intranuclear structures by its degradation with sphingomyelinase results in a loss of activities of both RNA polymerases. It is assumed that sphingomyelin plays a role in the transcriptional activity by changing the structure of the template and that of the enzymes.

Animals↗