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Iu I Mitrokhin

Publications and source records attributed to Iu I Mitrokhin.

At least 19 recordsLinked to original sources
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↗
PubMed1987

[Characteristics of [3H]cycloheximide distribution, protein and DNA biosynthesis in rat organs after sublethal blocking of translation].

The kinetics of accumulation and release of [3H]cycloheximide (CHI) as well as protein and DNA biosyntheses in some organs of the rats injected with sublethal doses of CHI were studied. It was shown that in the majority of organs under study (especially in the liver, kidneys and adrenals) the inhibition is completed within 12 hours after CHI injection followed by the resumption of protein and DNA syntheses. In the thymus and pancreas the levels of these biosyntheses remain below control values up to the 72nd hour. A positive correlation was observed between the decrease of CHI (or its metabolites) concentration and the beginning of protein and DNA syntheses in different organs. However, there was a reverse correlation between the high values of squares below the kinetic curves of CHI release from the liver, kidneys and adrenals and the intensive resumption of protein and DNA biosyntheses in these organs. It was thus assumed that in these particular organs CHI is subjected to intensive biotransformations. The contribution of the endocrine system to the induction of intensive compensatory protein and DNA syntheses in the liver were estimated from the viewpoint of the nature of reconstructive processes occurring in the appropriate organs.

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

[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↗
PubMed1980

[Complex nature of the inhibitory effect of the cytosol on transcription in isolated nuclei of rat liver].

It was shown that rat liver cytosol contains a factor inhibiting [3H]UTP incorporation into RNA of isolated nuclei. Fractionation of cytosol by Sephadex G-100 chromatography, step-wise increase in ammonium sulfate concentration and electrophoresis in polyacrylamide gel revealed a complex nature of cytosol inhibitory activity. It was suggested that this complex nature can be due to the presence of either non-specific inhibitors of transcription (i.e. phosphatase, RNAase) or a set of virtually specific inhibitors of transcription in the cytosol.

Animals↗
PubMed1976

[Investigation of ribosomal RNAs from liver mitochondria of albino rats].

Study of sedimentation coefficients of rat liver mt-rRNAs labelled in vivo under conditions of selective inhibition by actinomycin D of nuclear RNAs biosynthesis, in hypoosmic system of isolated mitochondria, and of mt-rRNAs isolated from purified 55 ribosomes revealed that mt-rRNAs are represented by 16S and 12S components. Both components are found to be of AU-type. Anomalous behaviour of mtRNA on MAK columns is observed. Some aspects of isolation and identification of mt-rRNAs in higher organisms are discussed.

Animals↗
PubMedDate not supplied

[RNA biosynthesis in mitochondria under conditions of prolonged inhibition of protein biosynthesis in rat liver cytoplasm].

When cytoplasmic protein synthesis is inhibited by cycloheximide (CHI) in vivo synthesis of water-soluble mitochondrial proteins and of mitochondrial RNA is decreased. These changes measured in isolated rat liver mitochondria are similar to those observed in vivo and correlate with the changes the synthesis of water-soluble proteins in mitochondria. When the cytoplasmic fraction (30,000 g-supernatant) had been added to the mitochondria showing decreased RNA synthesis, the RNA synthesis increased to the control level (the incubation conditions were favourable for the protein transport from microsomes to mitochondria). RNA synthesis in mitochondria was not stimulated by cytoplasmic fractions from the CHI-pretreated rats. After prolonged dialysis these fraction stimulated RNA synthesis even to a greater extent than cytoplasmic fractions from the untreated animals. Mitochondrial RNA polymerase activity (measured in mitochondrial extracts supplemented with exogenous DNA) was higher in extracts of mitochondria from livers of normal rats than in extracts of mitochondria from livers of animals injected with CHI.

Animals↗
PubMedDate not supplied

[Study of the ultrastructural and functional expression of the hepatocyte genome under conditions of prolonged depression of protein biosynthesis by cycloheximide. III].

Dynamics of changes in mtRNA synthesis and mitochondria ultrastructure is strictly dependent on the level of inhibition of biosynthesis of cytoplasm proteins and "soluble" proteins of mitochondria by cycloheximide in hepatocytes: 1-6 hrs later a progressive weakening of protein synthesis is accompanied by a drop in mtRNA synthesis and essential destruction of mitochondria; from 12 to 24 hrs a partial restoration of protein biosynthesis induces the processes of the above-mentioned indexes normalization.

Animals↗
PubMedDate not supplied

[Ecdysterone modulates antitumor activity of cytostatics and biosynthesis of macromolecules in tumor-bearing animals].

The influence of therapeutic and half doses of cisplatin and adriamicin combination with the anabolic drug ecdisteron (20-hydroecdison) on development of subcutaneously and intraperitonially transplanted P388 and L1210 leukemia and metastasizing B16 melanoma was studied. Ecdisteron significantly stimulated the chemotherapeutic effect of low doses of the cytostatics: inhibition of tumor growth, mice survival rate, their lifespan, and the antimetastatic activity index were comparable or better than after therapy with high doses of the antitumor drugs. The influence of high and low doses of cisplatin and its low dose in combination with ecdisteron on the dynamics of protein and DNA biosynthesis in the liver, pancreas, thymus, spleen, and adrenals of tumor-bearing mice were also studied. Although the therapeutic effect of 4 mg/kg cisplatin by activated protein biosynthesis and DNA repair is comparable or better than that of its low dose (2 mg/kg) in combination with ecdisteron, in terms of chemotherapy the combination looks preferable since the therapeutic dose of cisplatin is toxic for the intact tissues.

Adrenal Glands↗
PubMedDate not supplied

[Reaction of rats organ cells to inhibition of protein biosynthesis by sublethal doses of cycloheximide].

Time-dependent responses of cellular systems in rat organs and Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools in blood to the blocking of translation by sublethal doses of cycloheximide (CHI) was studied by EPR spectroscopy and radioisotope techniques. It was shown that, within the early post-CHI-treatment time, the suppression of deoxyribonucleotide and DNA biosynthesis, the activation of catabolic enzymes, the inhibition of electron transfer in the mitochondrial electron transport chain, the activation and the following inactivation of cytochrome P-450, and an intensive production of nitrosyl complexes in rat blood and organs occur. In addition, the activation of the synthesis of steroid hormones in adrenal gland was revealed within 1-24 h after cycloheximide injection. In response to these metabolic disturbances, nonspecific compensatory recovery reactions developed, first of all, the "reprograming" of the translation process to produce new protein-synthesizing elements instead of cycloheximide-blocked ones. The activation of protein synthesis promotes the recovery of deoxyribonucleotide and DNA synthesis, the restoration of the redox state of mitochondrial and microsomal electron transport chains in organs as well as an increase of Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools in rat blood. These metabolic processes result in the full recovery of the functional ability of organs.

Animals↗
PubMedDate not supplied

[Anabolic effect of natural and synthetic antioxidants].

The order of responses of cell systems of organs and changes in the content of some proteins of mouse and dog blood in response to addition of natural (alpha-tocopherol) and synthetic (ionol) antioxidants was studied at the whole-body level using ERP spectroscopy, radioisotope analysis, and chemiluminescence technique. Responses were evaluated by the temporary and concentration-dependence changes in the activity of ribonucleotide reductase and the rate of protein and DNA synthesis in organs of mice, as well as by the changes in the pools of Fe3+ -transferrin and Cu2+ -ceruloplasmin in blood and the antiradical activity of blood plasma of dogs and mice. During the first 24 h of exposure to alpha-tocopherol, the activity ribonucleotide reductase in bone marrow rapidly increased, whereas the activity of this enzyme and the rate of DNA synthesis in the thymus and spleen were suppressed by 30-50% compared to the control. The changes in these parameters had a phase mode with maxima on days 2-3 and 6-8. The stimulatory effect of the antioxidant on the processes of synthesis was concentration-dependent. We found that the optimal stimulation of the synthesis of deoxyribonucleotides, DNA, and protein was achieved by single administration of alpha-tocopherol at a dose of 20 mg per dog with an average weight of 15 kg and 17 mg/kg in the case of mice. Single or repetitive administration of higher doses of alpha-tocopherol was either ineffective or even suppressed the synthesis of DNA and deoxyribonucleotides. Ionol administered at a dose of 60 mg/kg increased DNA and protein synthesis in mouse organs in 2-4 and 1.2-1.5 times, respectively, compared to the control. It was also shown that single and repetitive administration of alpha-tocopherol to dogs increased the pool of Fe3+ -transferrin and Cu2+ -ceruloplasmin in blood in 2-3 times and by 20-30%, respectively, compared to the control. It is suggested that changes in Fe3+ -transferrin pool in peripheral blood may be used for evaluation of the stimulatory effect of antioxidants on the synthesis of macromolecules in organs and for the determination of dependence of this effect on the concentration of antioxidants.

Animals↗