ABSTRACT
The changes of kinetic characteristics (apparent Km and Vmax) of the Ca2+ phospholipid-dependent protein kinase (protein kinase C) from the rat liver for substrates ATP and histone Hl 2 and 24 hours after total X-ray irradiation have been established. The obtained results evidence for the important role of these changes in early radiosensitivity of protein kinase C.
Subject(s)
Liver/radiation effects , Protein Kinase C/radiation effects , Adenosine Triphosphate/metabolism , Animals , Histones/metabolism , Kinetics , Liver/enzymology , Rats , Time FactorsABSTRACT
Data about the influence of phosphorylation levels of histones isolated from the prereplicative and replicative phases induced to proliferation by cycloheximide of rat hepatocytes, on their interaction with DNA-cellulose are presented. It is shown that the DNA-cellulose chromatography of histones is a sensitive model for the investigation of the effect of phosphorylation of histones on their electrostatic interaction with DNA. Using this method it is possible to separate high-phosphorylated subtype of rat liver H1 histones from other subtypes and also to show a direct dependence between the phosphorylation levels of histones and stability of their binding with DNA in prereplicative and replicative phases not only under conditions of proliferation induction by cycloheximide, but also under the subsequent influence of X-irradiation and serotonin.
Subject(s)
Cellulose/analogs & derivatives , DNA/analogs & derivatives , Histones/metabolism , Liver/metabolism , Animals , Chromatography, Ion Exchange , Cycloheximide/pharmacology , Electrophoresis, Polyacrylamide Gel , Histones/isolation & purification , Phosphorylation , Rats , Serotonin/pharmacologyABSTRACT
It is established that local X-ray irradiation of the rabbit hind limb produces a decrease in Ca2+, Mg2+-ATP-dependent formation of electric potentials difference on the membrane of the sarcoplasmic reticulum (SR). These results agree with the observed decrease in the Ca2+-ATPase activity of SR membranes and increase in their electric conduction after irradiation.
Subject(s)
Calcium-Transporting ATPases/antagonists & inhibitors , Radiation Injuries, Experimental/enzymology , Sarcoplasmic Reticulum/enzymology , Animals , Calcium-Transporting ATPases/radiation effects , Membrane Potentials/radiation effects , Rabbits , Sarcoplasmic Reticulum/physiology , Sarcoplasmic Reticulum/radiation effects , Time FactorsABSTRACT
The modification of precipitation method for detecting DNA damage in mammalian cells using fluorimetric assay with 3.5-diaminobenzoic acid has been suggested. This modification allows determining DNA single- and double-strand breaks in mammalian nonproliferating cells and tissues. The influence of ionizing radiation upon the DNA damage in lymphoid cells of rat's spleen and thymus has been studied.
Subject(s)
DNA Damage , Lymphocytes/radiation effects , Spleen/radiation effects , Thymus Gland/radiation effects , Animals , Cell Division/genetics , Cell Division/radiation effects , Chemical Precipitation , Fluorometry , Mutagens , Rats , Spleen/cytology , Thymus Gland/cytologyABSTRACT
There forms of histone-specific acetyltransferases--A, B and C are obtained from the rat liver nuclei. The isolation process included nuclei generation, ammonium sulphate salting-out of proteins, DEAE-cellulose, hydroxyl-apatite, phosphocellulose chromatography and Sephadex C-200 gel-filtration. Acetyltransferases A, B and C from the nuclei were purified 56.8, 144.1 and 42.3 times, respectively. Histones were preferential substrates of the obtained enzymes. Molecular mass of acetyltransferases was determined by Sephadex G-150 and G-200 gel-filtration. It was 120 for enzyme A, about 90 for B and above 200 kDa for C.
Subject(s)
Acetyltransferases/isolation & purification , Liver/enzymology , Saccharomyces cerevisiae Proteins , Animals , Chromatography, DEAE-Cellulose , Chromatography, Gel , Chromatography, Ion Exchange , Histone Acetyltransferases , Molecular Weight , RatsABSTRACT
The model of impulse translation inhibition by cycloheximide in the rat liver was used for studying the combined and separate effect of serotonin and irradiation on the intensity of synthesis of chromatin proteins (histones and nonhistone proteins). Irradiation induces a considerable inhibition of the protein synthesis intensity, while serotonin has a contrary action, that under conditions of subsequent irradiation provides an increase in the synthesis level of histones and nonhistone proteins. Possible mechanisms of the irradiation and serotonin effect on the synthesis processes of chromatin proteins in the organism are discussed.
Subject(s)
Chromatin/metabolism , Cycloheximide/pharmacology , Liver/metabolism , Radiation-Protective Agents/pharmacology , Serotonin/pharmacology , Animals , Chromatin/drug effects , Chromatin/radiation effects , Chromosomal Proteins, Non-Histone/biosynthesis , Chromosomal Proteins, Non-Histone/radiation effects , Histones/biosynthesis , Histones/radiation effects , Liver/drug effects , Liver/radiation effects , Male , Rats , Whole-Body IrradiationABSTRACT
The paper deals with the influence of the X-irradiation and serotonin, as a radioprotector, on the chromatin protein methylation. It is shown that the X-irradiation and serotonin cause changes in the intensity of chromatin protein methylation in vivo, that may be explained by their effect on the activity of the corresponding methylases. Possible relationships between the changes in methylation of chromatin proteins and the general response of the organism to the irradiation, including administration of the radioprotector is under discussion.
Subject(s)
Chromatin/radiation effects , Nucleoproteins/metabolism , Protein Methyltransferases/metabolism , Radiation-Protective Agents , Serotonin/pharmacology , Animals , Chromatin/drug effects , Chromatin/metabolism , Male , Methylation , RatsABSTRACT
The paper deals with modern ideas of ways and mechanisms for realization of the radioprotector antiradiation effect. The data on the effect of biogenic amines (serotonin in particular) and radiation on the cAMP system are analyzed. It is shown that one of the most important mechanisms of the radioprotective effect is realized by changing the levels of histones and nonhistone proteins modifications through the adenylate cyclase system which leads to regulation of the chromatin template activity.
Subject(s)
Adenylyl Cyclases/metabolism , Cyclic AMP/radiation effects , Nucleoproteins/metabolism , Adenylyl Cyclases/radiation effects , Animals , Biogenic Amines/pharmacology , Chromatin/metabolism , Chromatin/radiation effects , Serotonin/pharmacology , Templates, GeneticABSTRACT
Content, methylation and an intensity of restoration of phosphoric components of ATP were studied in cross-striated muscles, brain and liver tissue of normal animals. These patterns were also studied in animals, subjected to irradiation: within 3 hrs after X-ray treatment (800 r); with subcutaneous administration of prozerine (0.5 mcg/kg) and nicotinic acid (20 microng/) 4 hrs before decapitation; and also in animals with vagus, cut off at the level of neck two weeks before irradiation. In different experimental conditions the character of regularity and interrelation between methylation and phosphorylation of ATP were established.
Subject(s)
Adenosine Triphosphate/metabolism , Radiation Injuries, Experimental/metabolism , Animals , Brain/metabolism , Liver/metabolism , Muscles/metabolism , Neostigmine/pharmacology , Nicotinic Acids/pharmacology , Oxidative Phosphorylation , Phosphorus/metabolism , Rats , VagotomyABSTRACT
The activity of enzymes of the antioxidation system and the content of some lipid peroxidation products in the liver and thymus of irradiated (0.21 C/kg) rats have been investigated. Glutathione reductase and glutathione transferase activity in the liver and thymus of rats decreased during the first 24 h after irradiation. There was a phase change in the catalase activity during the initial postirradiation period. The content of malonic dialdehyde increased immediately after irradiation and somewhat decreased during the first 24 h. In 24 h, there observed a radiation-induced increase in the diene conjugate content in the liver and thymus of rats, against the background of low activity of such antioxidation system enzymes as glutathione transferase, glutathione reductase and catalase.
Subject(s)
Catalase/analysis , Glutathione Reductase/analysis , Glutathione Transferase/analysis , Lipid Peroxidation/radiation effects , Liver/radiation effects , Thymus Gland/radiation effects , Animals , Female , Liver/enzymology , Liver/metabolism , Male , Malondialdehyde/analysis , Rats , Rats, Inbred Strains , Thymus Gland/enzymology , Thymus Gland/metabolism , Time FactorsABSTRACT
The content of malonic dialdehyde, dienic conjugates and free fatty acids, and catalase activity were determined in some organs and tissues of chronically irradiated rats. Certain regularities were found in lipid metabolism changes. The MIGI-K preparation was shown to normalize some indices under study.
Subject(s)
Accidents , Catalase/radiation effects , Fatty Acids, Nonesterified/radiation effects , Lipid Peroxidation/radiation effects , Nuclear Reactors , Power Plants , Animals , Catalase/drug effects , Catalase/metabolism , Environmental Exposure , Lipid Peroxidation/drug effects , Lipid Peroxides/metabolism , Lipid Peroxides/radiation effects , Male , Malondialdehyde/metabolism , Malondialdehyde/radiation effects , Radiation-Protective Agents/pharmacology , Rats , UkraineABSTRACT
Using an acellular system, with isolated chromatin as a template, and E. coli RNA-polymerase it was shown that irradiation of rats with a lethal dose (7.76 Gy) caused a progressing, in time, decrease in the inhibitory effect of H1, H2a, H2b, H3 and H4 histones (particularly H2a histone) on RNA synthesis. The administration of serotonin prior to irradiation diminished considerably this effect of radiation.
Subject(s)
Radiation Injuries, Experimental/genetics , Radiation-Protective Agents/therapeutic use , Serotonin/therapeutic use , Transcription, Genetic/radiation effects , Animals , Cell-Free System , Histones/genetics , Liver/radiation effects , Radiation Injuries, Experimental/prevention & control , Rats , Transcription, Genetic/drug effectsABSTRACT
One and 24 h following single X-irradiation (0.21 C/kg) of rabbit hind leg the content of free fatty acids and phospholipid lysoforms increased in the sarcoplasmic reticulum (SR) membrane of skeletal muscles. The results obtained are important in estimating the mechanisms of action of ionizing radiation on the structural and functional properties of SR.
Subject(s)
Fatty Acids, Nonesterified/radiation effects , Intracellular Membranes/radiation effects , Membrane Lipids/radiation effects , Phospholipids/radiation effects , Radiation Injuries, Experimental/metabolism , Sarcoplasmic Reticulum/radiation effects , Animals , Chromatography, Thin Layer , Fatty Acids, Nonesterified/analysis , Female , Intracellular Membranes/analysis , Male , Membrane Lipids/analysis , Phospholipids/analysis , Rabbits , Sarcoplasmic Reticulum/analysis , Time FactorsABSTRACT
The cycloheximide block model was proposed to study the mechanism of action of both radiation and radioprotectors. It was shown that irradiation of proliferating hepatocytes in vivo, at early stages of the prereplicative phase, markedly inhibited DNA synthesis. Serotonin, in its turn, considerably increased DNA synthesis maintaining this increase after subsequent exposure to X-radiation.
Subject(s)
DNA/biosynthesis , Liver/metabolism , Radiation Injuries, Experimental/metabolism , Radiation-Protective Agents/therapeutic use , Serotonin/therapeutic use , Animals , Cycloheximide/pharmacology , Liver/drug effects , Liver/radiation effects , Male , Radiation Injuries, Experimental/prevention & control , RatsABSTRACT
The radiation injury affects the quantitative ratio of histone fractions. The most pronounced changes in the percentage content towards a decrease are observed for the fractions F2a1 and F2a2 as well as for F2a 12 h and 24 h after irradiation, respectively. An increase by 41.8% is observed in the content of the fractions F2b+F3 12 h after irradiation. The methylation for all histones of the fractions increases considerably 2 h after irradiation, drops 12 h later in the fractions F2a1 and F3 and 24 h later in the fractions F3 and F1 as compared to the normal level.
Subject(s)
Histones/radiation effects , Liver/radiation effects , Radiation Injuries, Experimental/metabolism , Animals , Cell Nucleus/radiation effects , Chemical Phenomena , Chemistry , Histones/metabolism , Methylation , Rats , X-RaysABSTRACT
Phosphorylation and synthesis of histones and nonhistone proteins were studied after the inhibition of translation by sublethal cycloheximide doses. Activation of the chromatin protein phosphorylation was noted: (1) at the stage of recovery and stimulation of the protein synthesis (18-24 h), and (2) at the stage of activation of the replicative DNA synthesis (30-60 h). Phosphorylation and synthesis of the chromatin proteins depended upon the individual or combined effect of X-radiation and serotonin. The authors discuss the possible role of the chromatin protein phosphorylation in the response of the nuclear apparatus to the effect of radiation and serotonin the latter being used as a radioprotective agent.
Subject(s)
Chromosomal Proteins, Non-Histone/biosynthesis , Cycloheximide/pharmacology , Histones/biosynthesis , Liver/radiation effects , Serotonin/pharmacology , Animals , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cell Nucleus/radiation effects , Chromatin/drug effects , Chromatin/metabolism , Chromatin/radiation effects , Chromosomal Proteins, Non-Histone/radiation effects , DNA Replication/drug effects , DNA Replication/radiation effects , Histones/radiation effects , Liver/drug effects , Liver/metabolism , Male , Phosphorylation , Rats , Time FactorsABSTRACT
Changes in cAMP and cGMP levels after X-irradiation and radioprotective treatment with serotonin were studied using a model of impulse inhibition and repair of transcription, translation and replication by cycloheximide in rat hepatocytes in vivo. Irradiation was shown to inhibit the cyclic nucleotide synthesis. Serotonin increased the contents of cAMP and cGMP maintaining their elevated level after X-irradiation.
Subject(s)
Cyclic AMP/radiation effects , Cyclic GMP/radiation effects , Liver Regeneration/radiation effects , Radiation-Protective Agents , Serotonin/pharmacology , Animals , Cycloheximide/pharmacology , Liver/drug effects , Liver/metabolism , Liver/radiation effects , Liver Regeneration/drug effects , Male , Rats , Time FactorsABSTRACT
A preparation from mussels, MIGI-K, used as an additive to the diet of people working at the Chernobyl power plant has proved to be efficient in increasing the total resistance of the body, including the resistance to ionizing radiation. In experiments with animals, MIGI-K has been shown to accelerate excretion of 45Ca and 86Rb from the body. The combination of these properties of MIGI-K permits us to consider it an efficient drug to be used within the regions affected by the Chernobyl disaster.