Biomedical subjects
Publications and source records attributed to G F Zhegunov.
At the rat body temperature below 19 degrees C, their heart modifies its action and preserves physiological properties. The heart resistance against cooling during prolonged sleep seems to be due to a high stability of Ca-pump SR membranes.
The intensity of [14C]leucine incorporation into heart, liver, brain, muscle, and blood plasma protein in gophers under deep artificial hypothermia has been studied. It was shown that the intensity of protein synthesis decreased sharply under these conditions. Insignificant incorporation of [14C]leucine into proteins was observed during the first two hours after the onset of hypothermia and then ceased completely.
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The heart of ground squirrels is covered by a large amount of brown adipose tissue during the whole period of hibernation. During arousal and rewarming of heterothermal rodents, the highest temperature is detected in the brown adipose tissue and in the heart. During hibernation the heart rate is 10-12/min. On arousal, beginning from the early stage when the heart temperature is still low, a significant increase in the heart rate occurs followed by acceleration of the body rewarming of heterothermal animals.
A significant increase in protein synthesis correlating with ultrastructural dynamics of cardiomyocyte organelle convertions has been demonstrated in cardiomyocytes of ground squirrel during arousal from hibernation. In hibernating ground squirrels, the ultrastructure of protein-synthesizing organelles and of the cardiomyocyte nucleus points out to the readiness of cells to active synthesis of proteins. In the perinuclear area of cardiomyocytes abundant ribosomes, elements of endoplasmic reticulum and Golgi complex, mitochondria and high-energy substrates--glycogen and lipid inclusions--are seen. The cardiomyocyte nuclei are large, with highly convoluted borders and abundant pores, their nucleolar structure is granular, the chromatin is mainly diffuse. The potency of cardiomyocyte protein-synthesizing system of hibernating ground squirrels is realized every time at periodical arousals during hibernation. The role of cyclic changes of protein synthesis rate in adaptation of cells of hibernating mammals to functioning at various temperatures is discussed.
It was shown by electron microscopy that a highly convoluted sarcolemma, its numerous invaginations, well developed T-system contacting mainly with myofibrillar mitochondria and Z-zones were characteristic of cardiomyocytes of hibernants. In these cells lipid inclusions amounted as much as 3-4% of the cytoplasm. Cardiomyocytes of the arousing ground squirrels often revealed a complex of structures in the perinuclear area, responsible for protein synthesis and vesicle formation. Along with it the number of vesicles, including delineated ones, the majority of whom are contacting the sarcolemma, were manifested in the cell near-membrane area. A possible mechanism of cardiomyocyte plasma membrane rearrangements in ground squirrels and of alteration of their properties at the arousal, through a gradual replacement of plasma membrane material for the cytoplasmic vesicle bilayer, is discussed.
The structure and functions of the Ca-transport system of sarcoplasmic reticulum (SR) at low temperatures (-5--196 degrees) were studied. It was shown that during SR freezing-thawing the activation energy of ATP enzymatic hydrolysis as well as the Ca-ATPase sensitivity to calcium ions were changed. The Km value for the carrier seemed to be unaffected thereby. Using the EPR method it was shown that after freezing down to -196 degrees and a subsequent thawing the protein-lipil interactions and the orderliness of phospholipid fatty acid chains in the SR membranes were altered. On the contrary, the activity of Ca-ATPase isolated from SR membranes remained unchanged, which is indicative of the enzyme resistance to the cold. The mechanisms responsible for the impairment of the functioning of Ca-transport system of SR membranes due to freezing are discussed.
The effect of glucosamine on the transport of amino acids and protein synthesis in hepatocytes when modelling inflammation was studied. It was found the considerable decrease of the amino acid transport via hepatocyte membranes. The protein synthesis intensity was displayed as also significantly reduced. Administration of glucosamine to the rats normalized both studied processes.
Intensity of synthesis of total proteins and spectrum of synthesized proteins has been studied in various organs and tissues of sharp-faced frogs during local profound cooling of one of its limbs. It was shown that the effect of low temperatures on a certain part of a body of a poikilothermic animal has induced both a response of the whole organism and a much more acute response of the cooled tissues. The organism responded by a fall of the whole body temperature and a decrease in the activity of synthesis of total proteins of the viscera. Local cooling of a part of the frog body has induced a more significant decrease in the protein synthesis intensity in the cooled tissues alteration in the spectrum of synthesized proteins and appearance of specific proteins.
It was shown that the intensity of protein synthesis in cells of frogs, acclimated to 5 degrees C, is maintained at a high level, which is only 1.5-2 folds lower than that in animals acclimated to 20 C. In the process of acclimation to cold the intensity of synthesis decreases rapidly and already after 5 hours comprises one half of the value, which is characteristic of "warm" frogs, and the intensity of the process decreases more rapidly than the temperature of organs. On acclimation to warmth the intensity of protein synthesis increases and is getting stabilized at the level, characteristic of "warm" amphibia in 10-15 hours. It was shown that under various temperature conditions or conditions of acclimation specific proteins were synthesized against a background of the main groups of proteins.
The effect of rapid freezing down to--196 degree C was studied as applied to the functional activity of sarcoplasmic reticulum (SR) membranes Ca2+-pump. It is found that the SR Ca-transport system is damaged under the effect of low temperatures: the transport activity of Ca ions across the reticulum membrane is reduced simultaneously with a slight increase in the ATPase activity. The rate of Ca ions accumulation by SR vesicles decreases and the magnitude of Ca: ATP ratio is reduced. The damage of the SR membrane Ca-transport system after freezing is related to an increase in the rate of the accumulated Ca2+ rapid leak from the vesicles through the system of active transport at the moment of ATPase "work" and to an increase in the rate of passive diffusion.
It has been demonstrated that during winter hibernation (body temperature 2-4 degrees C), the heart rate in ground squirrels is equal to 100 10-12 beats/min. At the initial stage of the arousal, while body temperature remains still low (9-10 degrees C), the heart rate may increase up to 160-200 beats/min. At this stage, practically all electrophysiological parameters of the heart correspond to those in active animals. These results may indicate the ability of "cold" heart in arousing ground squirrels to operate as a normothermic organ and reveal certain role of the heart in body warming. Significant increase of the intensity of protein synthesis in cardiomyocytes together with periodic changes in protein composition of their membranes were found during arousal which may account for regulation of the level of metabolism in cells and for adaptation of the latter to different temperatures.
Studies have been made on the ultrastructure of cardiomyocytes during hibernation and arousal of the ground squirrel C. undulatus. It was found that the number of elements of the rough endoplasmic reticulum, Golgi complex, vesicles and ribosomes increases in the perinuclear areas of cardiomyocytes during arousal of animals. These areas are saturated with lipid inclusions and mitochondria. Numerous vesicles and fringed bubbles were found near the plasma membrane which has many caveolae. These findings may indicate the intense metabolism of the membrane material between plasmalemma and cytoplasmic vesicles. Possible mode of rapid reorganization of the sarcolemma and changes in its functional properties during hibernation-arousal stages are suggested. It is concluded that apart from structural and functional properties which are acquired by cells during preparation of animals to hibernation and which exhibit only small changes during the whole period of hibernation, cyclic changes in plasmalemma structure and function occur during arousal of the ground squirrels.
Intensity of the protein synthesis is studied in cells of different organs and tissues of hibernating, arousing and active gophers and rats. It is established that during hibernation a level of labelled aminoacids incorporation into proteins of all organs under study (ventricle, auricle, liver, spleen, diencephalon, adrenal gland, brown fatty tissue) is inconsiderable. The protein synthesis intensity essentially grows after animals arousing and their body temperature elevation, ten times exceeding the level of the studied process in hibernating gophers. Rate of precursors' incorporation in cell proteins of active gophers and rats is 3-4 times lower than in arousing rodents. The same regularity is revealed when studying rates of labelled amino acids incorporation into slices of the above organs and tissues.
Freezing-thawing of rat liver mitochondria evokes a release of Ca2+ into the incubation medium containing oxidation substrates: succinate and phosphate. The release is accompanied by a decrease in the membrane potential value. ATPase and NADH-dehydrogenase inhibitors when introduced into the medium simultaneously with mitochondria prevent the both processes, but only till Ca2+ release. ADP added during Ca2+ release, initiates its uptake. When succinate is replaced by NAD-dependent substrates (malate in combination with glutamate) and in the presence of the antioxidant (ionol) Ca2+ is not released from mitochondria. It is supposed that Ca2+ release from mitochondria due to freezing-thawing is evoked by activation of lipid peroxidation and is controlled by the degree of pyridine nucleotide reduction.
Synthesis intensity and a spectrum of synthetized proteins of blood plasma in the gophers at different hibernation stages (hibernation, awakening, being awake) were studied. It is established that the organism of hibernating animals has a constant concentration of plasma proteins during the whole period of the winter hibernation. Selective activation of synthesis of certain groups of plasma proteins is observed at different stages of hibernation in gophers and certain amount of specific proteins appear.
The intensity of labelled leucine penetration from the blood-circulating system to the tissues and its incorporation into proteins of some organs of gophers have been studied under hibernation and hypothermia. It is shown that, in spite of the low temperature of the gopher body under hibernation, the intensity of amino acids transfer from the blood to the tissue was approximately the same as in active state. But the rate of proteins synthesis under hibernation considerably decreases though it is not completely stopped. Under artificial hypothermia of the mammals the transition of amino acids from the blood to the tissue is considerably hampered. Under these conditions the incorporation of labelled amino acids is completely stopped.