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Biomedical subjects

I N Todorov

Publications and source records attributed to I N Todorov.

At least 19 recordsLinked to original sources
PubMed1999

The activation of ribonucleotide reductase in animal organs as the cellular response against the treatment with DNA-damaging factors and the influence of radioprotectors on this effect.

Cellular requirements for deoxyribonucleotide (dNTP) pools during DNA synthesis are related to ensuring of the accuracy of DNA copying during replication and repair. This paper covers some problems on the reactions of dNTP synthesis system in organs of animals against the treatment with DNA-damaging agents. Ribonucleoside diphosphate reductase (NDPR) is the key enzyme for the synthesis of dNTP, since it catalyses the reductive conversion of ribonucleotides to deoxyribonucleotides. The results obtained show that the rapid and transient increase in NDPR activity in animal organs occurs as cellular response against the treatment with DNA-damaging agents (SOS-type activation). We have also found the intensive radioprotector-stimulated activation of deoxyribonucleotide synthesis as well as DNA and protein synthesis in mice organs within 3 days after the administration of two radioprotectors, indralin and indometaphen, that provide the high animal survival. Our studies suggest that these effects are the most important steps in the protective mechanism of the radioprotectors and are responsible for the high animal survival.

Animals↗
PubMed1991

[Effects of cycloheximide on protein, RNA and DNA synthesis in cultures of CHO cells and human diploid fibroblasts].

In CHO cell line and primary human diploid fibroblasts culture an incorporation of protein, RNA and DNA biosyntheses precursors was investigated under different conditions of inhibition of translation by cycloheximide (CHM). Both CHO and human fibroblasts transitory treatment by CHM in the serumfree medium resulted in inhibition of protein and DNA syntheses during S-period while RNA synthesis increased up to 130% (CHM concentration from 0.003 to 2 Mg/ml), as well as in Go--an incorporation of 3H-U increased to 200% (CHM concentration-100 Mg/ml). Long-term treatment (48 hours) in the serum-free medium resulted in decreased uptake of 3H-T and 3H-L during first 6 hours of experiment, while incorporation of 3H-U increased to 160%. By 16-th hour of treatment characters of protein, RNA and DNA syntheses came back to control levels.

Animals↗
PubMed1990

[Reorganization of chromatin superstructure during marked changes in the rate of protein synthesis].

The changes in the structure and RNA-polymerase activity of rat liver cell chromatin after a single injection of cycloheximide (3 mg/kg of body mass) were studied. The cycloheximide-induced fluctuations in protein synthesis rates are concomitant with episodes of drastic changes in the chromatin structure. The reorganization of the general protein structure is associated with an increase or a decrease of the RNA-polymerase II activity. The data obtained suggest that the activation-inactivation of RNA-polymerase II in cell nuclei is due to reorganization of chromatin infrastructures--from higher levels of the electron-dense chromatin package to the unfolded nucleosomes of the transcriptionally active protein.

Animals↗
PubMed1989

[Polyribosomes, isolated from rat liver in a low ionic strength medium, capable of autonomic translation in a cell-free system without the addition of cellular fluid].

Polyribosomes isolated from the liver in the presence of 10 mM KCl and purified by centrifugation through 2 M sucrose were shown to incorporate [3H]leucine both into aminoacyl-tRNA and polypeptides in a cell-free system without cell sap. The incorporation of [3H]leucine showed a linear increase within 80-100 min and was then levelled off. The system was sensitive to cycloheximide, puromycin and ethionine and needed ATP, GTP and unlabeled amino acids. The quantitation of tRNA in polyribosomes (the fraction which did not sediment with the subparticles after polyribosome dissociation) revealed more than two tRNA molecules per 80S monosome. It is likely that this tRNA excess as well as the earlier established presence of aminoacyl-tRNA synthetases and elongation factors promote the autonomic translation of polyribosomes.

Animals↗
PubMed1988

[Dynamics of the biosynthesis of components of the protein synthesizing apparatus of the rat liver at the stage of restoration of translation, inhibited by cycloheximide].

The biosynthesis of proteins, ribosomal RNA and other components of the rat liver protein-synthesizing system during the reparation and subsequent activation of translation inhibited by a sublethal dose cycloheximide (CHI, 3 mg/kg) was studied. It was found that the incorporation of labeled precursors into proteins and ribosomal rRNA isolated from free and membrane-bound polysomes is repaired already 3 hours after CHI injection. 6-9 hours thereafter, the level of component labeling reaches control values, whereas the total protein biosynthesis is retarded. After 12-24 hours, marked stimulation of ribosome biosynthesis and the integration of ribosomes into polysomes are observed together with an asymmetric accumulation of excessive amounts of newly synthesized 40S subunits into polysomes 12 hours after CHI infection. The putative mechanisms of the activation of expression of the part of the genome responsible for protein and ribosomal rRNA synthesis as well as for the synthesis of other components of the protein-synthesizing system are discussed.

Animals↗
PubMed1988

[Rat liver energetics according to data of 31P-NMR in extreme states of the processes of biosynthesis of proteins and nucleic acids].

The dynamics of phosphomonoesters, phosphodiesters, Pi, ATP, ADP, NAD(H+) and uridine diphosphoglucose (UDPG) levels in rat liver upon sharp oscillations in the rates of protein and nucleic acid biosynthesis induced by a sublethal++ dose of cycloheximide was studied, using the 31P-NMR method. The results obtained with preparations of native liver are unaffected by fractionation, homogenization and chemical extraction procedures. It was demonstrated that oscillations of Pi, ATP and UDPG levels in liver cells reflect the changes in the energy consumption and intracellular energy-linked processes (e.g., glycolysis, oxidative phosphorylation, glycogen synthesis and consumption) under conditions of variable macromolecular synthesis rates. The oscillations in phosphomonoesters and phosphodiesters levels are mainly due to cycloheximide-induced lipid metabolism disturbances.

Animals↗
PubMed1986

[Correlation of the activity of the key enzymes of glycolysis and respiration in hepatomas with different growth rates].

It is shown that an increase in the activity of glycolysis resulting from the rise of the hepatoma growth rate is accompanied by a decrease in the activity of the pentose-phosphate pathway and respiratory chain. It is supposed that variations in the activity both of different carbohydrate catabolism ways and the respiration with a rise of the hepatoma growth rate reflect changes in the relative content of cells at different phases of the cell cycle.

Animals↗
PubMed1986

[The 31P-NMR study of the metabolism of phosphate-containing compounds in the rat liver during inhibition of protein synthesis].

Using the 31P-NMR method, the composition of the pool of phosphate-containing metabolites in intact rat liver 72 hours following the blocking of protein biosynthesis by cycloheximide was studied. It was shown that during maximal inhibition, i.e., 2-3 hours after cycloheximide injection, the ATP concentration decreases approximately 5-fold, that of ADP and sugar phosphates--4- and 2-fold, respectively. The intracellular pH in hepatocytes was followed by measuring the chemical shift of the Pi signal. The reconstitution of intracellular pH after 2-3 hours is consistent with changes in the Pi level in hepatocytes. The experimental results were compared with the data of biochemical analysis. NMR seems to be a promising tool in the study of metabolism of various animal organs and tissues under physiological and pathological conditions.

Animals↗
PubMed1985

[Sequential changes in the macrostructure and RNA-synthesizing activity of nucleolar and extranucleolar chromatin from rat liver cells during induction of DNA synthesis].

The dynamics of structural changes and RNA-polymerase activity in rat liver cell chromatin caused by drastic changes in the rates of protein synthesis was investigated. Inhibition of protein synthesis after a single injection of animals with cycloheximide (0.3 mg/100 g of body weight) increased the total condensibility of chromatin. Under these conditions, the stepwise activation of RNA-polymerases I and II correlated with decondensation of chromatin. By the 6-12th hour following cycloheximide injection, a chromatin fraction enriched with RNA-polymerase I and a RNA-polymerase II-rich fraction could be isolated from liver cell nuclei.

Animals↗
PubMed1985

[Metabolism of 18S-rRNA in rat liver cells in different functional states of the protein-synthesizing apparatus].

The ratio of absolute radioactivities of 28S and 18S ribosomal RNA in membrane-bound and free polysomes and in free ribosomes of rat liver were studied under conditions of translation inhibition by cycloheximide, insulin and cAMP. Insulin and cAMP, in contrast with cycloheximide, did not induce selective degradation of 18S-rRNA. The data obtained are discussed in terms of the feasible role of S6 protein phosphorylation in degradation of the 40S ribosomal subunit.

Animals↗
PubMed1985

[Structural characteristics of DNA from the rat liver during inhibition of protein synthesis with cycloheximide].

At cot around 20, the rat liver DNA reassociation curves were obtained 12-48 hours after injection of the animals with sublethal doses of cycloheximide. In total preparations of DNA-24 and DNA-36 at cot 0.02-0.06, the number of fast reassociating sequences was increased, on the average, by 4%. The differences in reassociation rates for individual kinetic fractions are 2.5-3-fold. The total incorporation of the label into DNA-24 preparations is sharply decreased; however, a marked distinction in the incorporation between the fractions in parameter cot was observed.

Animals↗
PubMed1985

[Activation of nuclear polypeptide synthesis in rat liver cells after inhibition of template protein synthesis. The role of nuclear polypeptide synthesis in the changes of the chromatin structure].

The correlation between the rates of nuclear polypeptide synthesis (NPS) and matrix protein synthesis in rat liver cells was investigated. It was shown that NPS is activated under conditions of protein synthesis inhibition in the cytoplasm. Model experiments revealed that the NPS and ADP ribosylation systems compete for chromatin structure: ADP ribosylation induces condensation, while NPS--decondensation of chromatin.

Adenosine Diphosphate Ribose↗
PubMed1984

[Structural changes in chromatin during activation of transcription coupled with translation inhibition by cycloheximide].

A chromatin preparation isolated one hour after cycloheximide injection possesses a higher RNA-synthesizing activity and is split by DNAase I to a greater extent as compared to chromatin of control hepatocytes. Thermal denaturation of this preparation causes a considerable increase (about 2-fold) in the content of the thermolabile fraction melting in the free DNA denaturation zone. The relative content of fast repetitions in the thermolabile fraction (1 hour after the beginning of experiment) is lower than that in control. The type of changes in the viscosity of chromatin in the predenaturation zone isolated one hour later suggests a more labile binding of DNA to the protein. Chromatin preparation isolated 3 hours after cycloheximide injection is characterized by intermediate values of all parameters under study, as compared to the two other preparations used in this experiment. It is assumed that the activation of transcription coupled with the inhibition of translation by cycloheximide is determined by the appearance of elongated segments of free or weakly bound DNA in the chromatin preparation.

Animals↗
PubMed1984

[Relation of the biosynthesis of intracellular and export proteins in rat liver cells during induction of proliferation by cycloheximide].

After a single injection of a sublethal dose of cycloheximide (CHI) the biosynthesis of extracellular proteins in rat hepatocytes was rapidly suppressed, the reconstitution being very slow. On the contrast, the biosynthesis of intracellular proteins (e.g., histones, and other acid-soluble liver proteins) was more resistant to CHI. The activation of biosynthesis of acid-soluble and acid-insoluble proteins was found to occur stepwise. It was assumed that the activation of synthesis and accumulation of intracellular proteins after CHI release accompanied by a decreased synthesis of extracellular proteins is one of possible causes of stimulation of DNA synthesis in the hepatocytes following a single injection of CHI.

Animals↗