[The effect of surgical stress on DNA synthesis in liver and brain cells]. / Effekty operatsionnogo stressa na sintez DNK v kletkakh pecheni i mozga.

Distinct alterations in the rate of DNA synthesis (an increase in the rate of reparation and a decrease in the rate of replication in nuclei and mitochondria) were detected in liver and brain cells during the stress caused by surgical operation. Within 8-10 hrs after the operation the rate of DNA reparation was increased by 40-50% in nuclei of liver cells and by 31-35% in brain cell nuclei. Replication of nuclear DNA was decreased immediately after the operation--by 33% in liver cells and by 50% in brain cells. Within a day after the operation the rate of replication was restored up to the control level in liver cells, while it was still decreased by 30% in brain cells. The rate of mitochondrial DNA synthesis was slightly decreased within the first 12 hrs after the operation: by 12-14% in liver cells and by 18-20% in brain cells. The stress, and particularly postoperative stress, exhibited pronounced action on structure and various systems of DNA synthesis in cells of various tissues.

[Suppression of replication and activation of DNA reparative synthesis in stress and prevention of these phenomena by preliminary adaptation]. / Podavlenie replikatsii i aktivatsiia reparativnogo sinteza DNK pri stresse i preduprezhdenie étikh iavlenii predvaritel'noi adaptatsiei.

Effects of preliminary adaptation to short-term stress or to regular hypoxia on disturbances of DNA biosynthesis were studied in liver and heart tissues under conditions of emotional-painful stress (EPS). EPS was found to induced activation of DNA reparative synthesis in heart and liver tissues and affected dissimilarly DNA replication in these tissues: activation of the reaction in heart and suppression in liver tissue. Adaptation to regular hypoxia limited distinctly the burst of DNA reparative synthesis in cells of both these tissues, reduced activation of the DNA replicative synthesis in heart and prevented the stress induced depression of DNA replication in hepatic cell nuclei and mitochondria. Mechanisms of the hepatoprotective effect of adaptation to hypoxia is discussed.

[DNA synthesis in heart cells in its compensatory hyperfunction]. / Sintez DNK v kletkakh serdtsa pri ego kompensatornoi giperfunktsii.

In modelling compensatory hyperfunction of the heart (CHH) due to coarctation of the aorta, the replication rate in the nuclei of myocardial cells increases in 24 hours and becomes 20 fold the control values in 48 hours. The replication rate in myocardial mitochondria in CHH reduces at the beginning of hyperfunction but increases almost two fold in 48 hours. The DNA reparation rate in the nuclei of the myocardial cells does not change in CHH. The rate of this process, however, increases significantly (by 50-74%) in cardiac cells of animals subjected to operation but without coarctation of the aorta.

[Elimination of stress-induced activation of DNA reparative synthesis in the myocardium by increasing the load on the heart]. / Ustranenie stressornoi aktivatsii reparativnogo sinteza DNK v miokarde posredstvom uvelicheniia nagruzki na serdtse.

The rate of DNA reparative synthesis was studied in the nucleus of myocardial cells in the heart compensatory hyperfunction (HCH) induced by the aorta coarctation and in animals exposed to surgical stress without the aorta coarctation. It was established that both surgery and emotional painful stress activated the DNA reparative synthesis in myocardial cells. For example, 12-24 hrs following the surgery the DNA reparation rate exceeded control values by 50-74%. HCH induced no changes in the DNA reparation rate in nuclei of myocardial cells. The mechanism of stress-induced DNA damage is discussed and a hypothesis is put forward on stabilizing the effect of hyperfunction on the DNA structure.

[The effect of emotional-pain stress on the rate of DNA synthesis in heart and liver cells]. / Vliianie émotsional'no-bolevogo stressa na skorost' sinteza DNK v kletkakh serdtsa i pecheni.

Effect of a single long-term (6 hrs) emotional-painful stress on DNA synthesis was studied in nuclei and mitochondria of heart and liver cells. Various systems of DNA synthesis in heart and liver cells were shown to respond dissimilarly to the stress. The rates of replication and reparative synthesis of nuclear DNA were increased while synthesis of mitochondrial DNA was unaltered in heart cells within the first day after the stress. In liver cells the reparative synthesis of nuclear DNA was also increased, whereas the rate of its replication in nuclei and mitochondria was distinctly inhibited for a long time. Thus, the systems of DNA synthesis in liver cells proved to be more sensitive to extreme stress-reactions as compared with heart cells. Effect of the stress on the systems of DNA synthesis in specific and connective tissue cells of liver and heart is discussed. At the same time, mitochondria are localized in specialized cells of both heart and liver tissues. The data obtained suggest that inhibition of the mitochondrial DNA synthesis is realized in hepatocytes.

[The role of cytoplasmatic factors in post-stress changes in the RNA synthesis in the heart and liver]. / Rol' tsitoplazmaticheskikh faktorov v postsressornykh izmeneniiakh sinteza RNK v serdtse i pecheni.

Effect of protein factors from heart and liver cytoplasm (S-100 fraction) on activity of RNA polymerases I and II was studied in isolated nuclei of heart and liver tissues under conditions of immobilization stress. Activity of the cytosol factors, stimulating ribosomal RNA (rRNA) synthesis, was altered during the post-stressory period. Immediately after immobilization the activity of the cytosol was decreased at the catabolic phase. Within a day the activity was distinctly increased at anabolic phase of the stressory reaction. The active post-stressory cytosol was studied in the cell-free system containing nuclei from heart and liver tissues of animals subjected to stress and of the control animals. The active post-stressory cytosol increased the rate of rRNA synthesis in corresponding nuclei of heart and liver tissue, while synthesis of rRNA was increased 2-fold in nuclei of control animals as compared with heart and liver nuclei, isolated within a day after termination of stress. Activation of the cytoplasmic factors stimulating the transcription rate is concluded to be of importance for regulation of rRNA synthesis under adaptation conditions.

[Change in the RNA polymerase activity in heart and liver cells during immobilization stress]. / Izmenenie aktivnosti RNK-polimeraz v kletkakh serdtsa i pecheni pri immobilizatsionnom stresse.

Immobilization stress produces changes in the activity of polymerase I and II RNA in heart and liver cells. At the beginning of the poststressor reaction of the body the activity of both enzymes is lowered. Later on the activity of polymerase I RNA considerably exceeds the control level, whereas the activity of polymerase II RNA returns to the initial values.

[Participation of cytoplasmic factors in the rate of transcription in compensatory hyperfunction of the heart]. / Uchastie tsitoplazmaticheskikh faktorov v uskorenii transkriptsii pri kompensatornoi giperfunktsii serdtsa.

Effect of cytoplasmic fraction S-100 from normal heart and liver tissue as well as from the tissues at the period of compensatory growth, caused by hyperfunction, on the rate of transcription in isolated nuclei was studied. In normal state heart and liver cytoplasm contained factors, accelerating RNA synthesis in nuclei, while activity of RNA-polymerase I was increased most significantly in presence of these factors as compared with RNA-polymerase II. Activity of these cytoplasmic factors, accelerating transcription, was distinctly increased in heart hyperfunction and in the liver tissue remaining after partial hepatectomy. The heart and liver cytoplasmic factors proved to be of protein nature, they did not exhibit any tissue specificity and their activity correlated with the rate of cellular RNA synthesis. Activation of cytoplasmic protein factors, accelerating transcription, appears to be an important mechanism, initiating the RNA synthesis increase in response to elevation of a tissue physiological functions.

[Molecular mechanisms of myocardial hypertrophy and deterioration]. / Molekuliarnye mekhanizmy gipertrofii i iznashivaniia serdechnoi myshtsy.

The development of cardiac compensatory hypertrophy (CCH) during heart adaptation to increased load is conditioned by two simultaneous processes which are accelerated synthesis and slower degradation of protein. In CCH, increased protein-synthesizing capacity of the myocardium is based on accelerated transcription. At the same time, the rates of rRNA and mRNA degradation are increased at the emergency stage of CCH. Organ-nonspecific cytoplasmic protein factors are identified that take part in the mechanism which initiates accelerated transcription during CCH. Along with total transcription acceleration, a selective activation of structural genes which code the most effective isoenzymes occurs in the heart at the emergency stage. A standard complex of biochemical changes in myocardial metabolism is shown to occur at the stage of wear and during physiological ageing: RNA concentration is decreased, the rates of its synthesis and degradation are reduced, as are the rates of protein synthesis and degradation. At the same time, administration of tRNA to animals accelerates protein synthesis in such a heart.

[Ratio of the amounts of the mRNA poly A+/poly A- fractions in the myocardium and the life span of mRNA poly A+]. / Sootnoshenie kolichestiv fraktsii iRNK poli A+/A- v miokarde i prodolzhitel'nost' zhizni poli A+ iRNK.

Two mRNA fractions, poly A+ and poly A- were found in the rat heart muscle. They comprise 30 and 70% of the entire mRNA, respectively. The ratio of the mRNA poly A+ to poly A- in the myocardium does not change in physiological aging. According to the kinetics of labelled precursor incorporation into mRNA, the life span of the main mass of mRNA poly A+ in the myocardium is about 4 hours.

[Creatine phosphokinase activity and its isoenzymatic ratio in the myocardium in adaptation of the heart to prolonged loading]. / Aktivnost' kreatinfosfokinazy i sootnoshenie ee izozimov v miokarde pri adaptatsii serdtsa k dlitel'noi nagruzke.

Three isoenzymes of creatine phosphokinase (CPK) were detected in rat heart myocardium after electrophoretic separation of the enzyme in agarose gel: MM-isozyme, MB-isozyme and BB-isozyme. The ratios of their activities were 60 : 30 : 5. Total activity of CPK per unit mass of myocardium was increased as well as transformation of its isoenzyme spectrum occurred at the early step of heart adaptation to the increased loading caused by aorta contraction. Within the third day of the heart hyperfunction the BB-isozyme activity was as high as 15% in the heart, the hybrid MB-isozyme activity was increased up to 40% and relative activity of the main muscle MM-isozyme was decreased down to 45%. The relative increase in the activity of BB-isozyme appears to reflect the preferable accumulation of the most functionally effective short-living isoenzymes, which play the key role in adaptation of tissues and systems to long-term loading.

[Metabolism of myocardial poly A+-containing mRNA normally and in compensatory cardiac hyperfunction]. / Metabolizm poli-A+-soderzhashchei iRNK miokarda v norme i pri kompensatornoi giperfunktsii serdtsa.

Two fractions of mRNA--polyA+ and polyA- containing mRNA--were found in rat heart muscle by affinity chromatography using polyU cellulose. These fractions constituted 30% and 70% of total mRNA, respectively. The ratio of polyA+/polyA- mRNA was not altered in myocardium under heart hyperfunction and in physiological ageing. Duration of life of polyA+ containing mRNA was 4 hrs in normal heart. A; the beginning of myocardium hyperfunction the period of mRNA life was decreased down to 2-3 hrs; this pattern of mRNA life alteration did not differ from control one in prolonged heart hypertrophy within 6 months. The rate of polyA+ containing mRNA synthesis was increased by 70% at the early steps of heart hyperfunction as compared with normal state; it decreased below the normal state in long-term hypertrophy of myocardium. In development of heart hyperfunction acceleration of polyA+ containing mRNA synthesis was more distinct than an increase in rRNA synthesis.

[In vitro incorporation of labelled amino acids into heart muscle ribosomes at early and late stages of compensatory heart hyperfunction]. / Vkliuhnie in vitro mechenykh aminokislot v pibosomy cerdechnoi myshtsy na pannei i pozdnei stadiiakh kompensatornoi giperfunktsii serdtsa

The activity of a protein-synthesizing cell-free system from heart muscle was studied at early and late stages of compensatory heart hyperfunction. It was found that the incorporation of amino acids into heart ribosomes during 48 hours after the hyperfunction had been produced, increased by 30% as compared to the control. The incorporation of amino acids into heart ribosomes at the late stage of hyperfunction (after 6 months) was decreased by 46% as compared to the early stages. The addition of homologous tRNA to the cell-free system of protein synthesis under prolonged heart hyperfunction stimulated the incorporation of amino acids into the ribosomes by 40--50%.

[Influence of aging on synthesis and breakdown of RNA and protein in the myocardium]. / Vliianiia stareniia na sintez i raspad RNK i belkov v miokarde

The rate of decomposition of RNA and proteins in the heart muscle of aged rats, as well as the effect of t-RNA on the rate of translation in the reconstructed non-cellular system of protein synthesis were studied. The rate of decomposition of sarcoplasmatic and myofibrill proteins and RNA is known to be decreased in the heart muscle of old animals. The metabolic changes. The addition of homologous t-RNA to the non-cellular system of protein synthesis was shown to stimulate the incorporation of labelled amino acids into the ribosomes of the heart of old rats.

[RNA and protein metabolism in the myocardium in aging and long-term hyperfunction of the heart]. / Metabolizm RNK i belka v miokarde pri starenii i dlitel'noi giperfunktsii serdtsa

Metabolism RNA and proteins was distinctly altered in myocardium hypertrophied due to prolonged hyperfunction and in the heart muscle of aged rats. The following alterations were observed: decrease in RNA concentration and in the absolute rate of protein synthesis in vivo, decrease in incorporation of labelled amino acids into heart ribosomes in cell-free system, the distinct depression of RNA turnover. The data obtained suggest that prolonged heart hyperfunction and hypertrophy promote the myocardium impairment and hence the process of senescence in developed more rapidly than under normal conditions.