Том 12, № 3 (2018)

Bone marrow cells of mesenchymal origin play an important role in adaptation of physiological systems to space flight. Hematopoiesis, immunity, and homeostasis of bone tissue depend on their functional activity. An investigation that was carried out in the framework of the Bion and Bion-M programs showed a decrease of the number of rat bone marrow hematopoietic progenitors and the inhibition of lympho- and erythropoiesis when the granulocyte-macrophage linage was activated. A negative influence on nonhematopoietic bone marrow cells was also revealed. The pathogenetic influence of radiation and microgravity on the bone marrow progenitor cells has remained unclear so far. The goal of this research was to study the effect of a 30-day unloading and 6 days of γ-irradiation on rat bone marrow progenitor cells. The study was conducted on male rats of four groups: vivarium control (VC), hindlimb unloading (HU), irradiation (IR), and combined action (HU + IR). The following parameters have been examined: the number of bone marrow mononuclear cells, proliferative activity of marrow mononuclear cells, immunophenotype, number of hematopoietic CFU and CFU-f, and differentiation potency of hematopoietic and stromal bone marrow precursors. It was found that the cellularity and proliferation activity of rat bone marrow cells did not change under simulation of space flight. The number of CFU-f was decreased. Irradiation was accompanied by an increase in the hematopoietic cell share among total bone marrow mononuclear cells, while their activity was attenuated. The osteopotential of the stromal precursors was unchanged. Adipogenic differentiation was stimulated with irradiation. The functional activity of bone marrow progenitor cells was restored after 2 weeks of recovery. Thus, 30-day simulation of space flight factors negatively affected the morphofunctional properties of rat bone marrow progenitor cells. These effects were reversible upon 2 weeks of recovery.

The early posttransfusion period after acute blood loss using erythromass without ozone was characterized by decreased electrophoretic mobility of erythrocytes (EPME), ATP, 2,3-diphosphoglycerate (2,3- DPG) concentration, Na⁺-K⁺-ATPase activity, and increased concentration of malonic dialdehyde (MDA) and catalase activity in erythrocytes. Most parameters gradually were restored over 5 days, but a reduced concentration of 2,3-DPG was observed throughout the entire experiment with transfusion of erythromass without ozone. Transfusion of the ozonized erythrocyte mass 1 h after its administration caused an increase in 2,3- DPG concentration in erythrocytes circulating in the vascular bed. Twenty-four hours later, increased catalase activity, EPPE, and ATP concentration were registered, and, after 5 days, enhanced Na⁺-K⁺-ATPase activity was registered. Their values were maintained until the end of the experiment at a higher level than in animals that had undergone transfusion of the nonozonized erythromass. Ozonized erythrocyte mass improves the functional metabolic state of erythrocytes, promotes an earlier recovery of the oxygen transport in blood, and limits the damage to the microcirculatory bed of the myocardium and cardiomyocytes during blood loss.

It is known that apoptotic endonuclease G (EndoG) induces alternative splicing (AS) of telomerase catalytic subunit TERT (telomerase reverse transcriptase) mRNA and inhibits telomerase activity in tumor cells and activated human T cells. The aim of this study was to investigate the possibility of TERT mRNA AS induction and inhibition of telomerase activity by EndoG in activated mouse and rat lymphocytes. To induce EndoG expression, mouse and rat CD4⁺, CD8⁺ T cells, B cells, and NK cells were transfected with the pEndoG-GFP plasmid or incubated with the DNA-damaging agent cisplatin in vitro. The increase in the EndoG expression resulted in decreased expression of full-length active TERT variant, enhanced synthesis of the truncated splicing variant, and decreased telomerase activity. An increase in the EndoG expression, a change in the mRNA pool of TERT splicing variants, and inhibition of telomerase activity were observed in mouse and rat lymphocytes after cisplatin administration in vivo. Thus, EndoG is capable of inducing TERT mRNA AS and regulating telomerase activity in mouse and rat lymphocytes.

The structural changes in proteins of the contractile apparatus of muscle fiber and the violation of their function due to point mutations in these proteins can be a cause of many hereditary diseases of human muscular tissue. Some such diseases are cap-myopathy and distal arthrogryposis, which may be connected with tropomyosin mutations. The deletion of glutamic-acid residue at position 139 of β-tropomyosin leads to the development of cap-myopathy, and the replacement of arginine at position 91 with glycine in this protein is linked to distal arthrogryposis. To understand how the Arg91Gly and Glu139del mutations disrupt the coordinated work of the contractile system of muscle fibers, recombinant wild-type and mutant β-tropomyosins were overexpressed and incorporated into thin filaments of ghost-muscle fiber. Fluorescent probes of 1,5-IAEDANS or FITC-phalloidin were specifically linked to the Cys707 of the myosin subfragment-1 and the three neighboring actin monomers, respectively. The polarized-microfluorimetry technique was used to study the spatial arrangements of actin and myosin in mimicking different stages of the ATPase cycle (in the presence of ADP or ATP and in the absence of a nucleotide) at low and high concentration of calcium ions. Both mutations were shown to change the conformational rearrangements of the myosin head and actin in the ATP hydrolysis cycle, which may be caused by abnormal behavior of the mutant tropomyosins during regulation. The altered work of the contractile system may be a cause of muscle weakness in congenital myopathies associated with these mutations.

It is known that the replacement of easily utilizable glucose with sorbitol in a medium activates a large number of repressed genes and metabolic changes in Neurospora crassa, which manifest themselves at the cellular level in a considerable vacuolization of the cytoplasm. The study of the morphological parameters and growth characteristics of isolated apical fragments of N. crassa hyphae showed that, in sorbitol-containing medium, the isolation from the parent mycelium causes the same disturbances in the coordination of elongation, branching, and septation as those described by us earlier for the glucose-containing medium. The metabolic changes caused by the carbon source replacement do not affect the hyphal-segment size, the distance from the growth point to the first septum, and the morphology and distribution of nuclei.