Том 11, № 5 (2017)

Elaboration of new correction methods for microcirculatory disorders in the brain caused by persistent high blood pressure is important for both medicine and biology. We studied the influence of intracerebral transplantation of human mesenchymal stem cells (hMSCs) on the cerebral microcirculation in young (4 month) and mature (12 month) spontaneously hypertensive rats (SHRs). It was shown that hMSC transplantation increased the density of the microvascular network of young SHRs to 1.6 and 1.9 times the density of the arteriolar area of the microvascular network of the pia. The density of microvascular network of mature SHRs increased by 1.4–1.5 times after hMSC transplantation. The perfusion and tissue saturation of sensorimotor cortex of young SHRs restored to the level of young normotensive rats. In mature SHRs, the perfusion and tissue saturation of sensorimotor cortex did not increase. In conclusion, the intracerebral transplantation of hMSC almost completely restored microcirculation in the sensorimotor cortex of the brain of young SHRs and slightly improved microcirculation in mature SHRs.

The effect of cytokines (IL-2, IL-7, and IL-15) having a common γ-chain of receptors on the maturation and differentiation of CD3⁺CD45RA⁺CD4⁺/CD8⁺ lymphocytes in homeostatic cultivation model in vitro was analyzed. It was found that the maximum IL-2 concentration in the helper CD45RA⁺-T-cell population mediates an increase in the number of CD45RA⁺CD4⁺ T lymphocytes with the phenotype of mature and immature terminally differentiated TEMRA T cells. IL-15 leads to the production of lymphocytes with CD27^–CD62L⁺ phenotype (presumably, TEMRA, in which the CD62L expression persists). In the CD45RA⁺CD8⁺ T lymphocyte populations, the studied cytokines (IL-2, IL-7, and IL-15) initiate the production of mature TEMRA (E) T lymphocytes and memory T cells with the CD45RA⁻CD27⁺CD62L⁺ central phenotype (TCM).

The expression of genes responsible for the synthesis of essential proteins regulating the calcium-ion balance and ultrastructural characteristics of fast-twitch (m. extensor digitorum longus, EDL) and slow-twitch (m. soleus, SOL) skeletal muscles under prolonged exercise were studied in an experimental model of forced-swimming rats. A day after the end of the exercise, no significant changes in any of the five investigated genes were revealed in the SOL. A few triad elements (T-tubules and cisternae of sarcoplasmic reticulum) were revealed. A small number of excitation-contraction coupling (ECC) structures in the control and a slight increase in their amount after exercises were noticed. Polymorphism and mitochondrial defects within SOL muscles indicate the importance of these structures in the regulation of calcium balance. In EDL muscles, adaptation mechanisms are aimed mainly at pumping Ca²⁺ ions to the sarcoplasmic reticulum, where the main calcium buffer is calsequestrin. Expression of SERCA1 gene increased by an order of magnitude, and that of CASQ1 increased by three times. Electron microscopy showed a major role of triads in the maintenance of calcium homeostasis in the EDL muscles, as well as a greater destruction of these muscles compared to SOL after exhausting exercise. The high level of triads and a possible activation of the CICR (calcium-induced calcium release) mechanism in fast-twitch muscles can cause damage to them during exhausting exercise. Adaptation of SOL muscles is associated with structural rearrangements of the mitochondrial apparatus, while adaptation of the EDL muscles is caused by calcium removal from the sarcoplasm with Ca-ATPase and its retention in the sarcoplasmic reticulum by calsequestrin.

FtsZ is a highly conserved protein that performs one of the key roles in cell division of most prokaryotes. At the present time it is believed that the main role of FtsZ in the cells of the microorganisms studied (Escherichia coli, Bacillus subtilis, etc.) is to control the process of cell wall synthesis at the site of future septum. In this regard, the presence of FtsZ in the cells of mycoplasmas – bacteria that lack the cell wall, looks intriguing. In the present work we investigated the influence of FtsZ proteins of three mycoplasmas – Mycoplasma hominis, Mycoplasma gallisepticum and Acholeplasma laidlawii – on the cytokinesis of E. coli. FtsZ proteins were able to interact with the E. coli division machinery, including inhibiting the cytokinesis process, while demonstrating various patterns of distribution in the cell. The data obtained support the hypothesis that FtsZ plays a significant role in the division of mycoplasma cells.

The toxic and metabolic effects of antipsychotics on cells of hepatic origin have been studied in vitro using human hepatoblastoma cell line HepG2. The cells were cultured in the presence of two first- and second-generation antipsychotics, haloperidol and olanzapine, respectively, at concentrations that can exist in the blood, liver and other tissues with high lipid content when the drugs are used for therapeutic purposes. During cultivation in several periods, the products of carbohydrate and lipid metabolism were quantified, the activities of several enzymes in the culture medium were measured, and viability (proliferation) of cells was assessed with MTS assay. Both drugs were toxic to HepG2 cells, which was manifested in inhibition of proliferation and an increased alkaline phosphatase activity in the culture medium. The toxic action of olanzapine in the doses used was less significant than that of haloperidol. According to literature data, antipsychotics increase the expression of lipogenesis genes in cells of the central nervous system, adipose tissue and liver, which can lead to hyperlipidemia. However, we have not observed increased levels of total cholesterol, cholesterol of low and high density lipoproteins, and triglycerides in the culture medium of HepG2 cells in the presence of haloperidol and olanzapine. This may be associated with the fact that both drugs, which are cationic amphiphiles, are able to inhibit intracellular lipid trafficking. Moreover, both drugs had no effect on the activity of aspartate aminotransferase and gamma-glutamyltransferase in the culture medium, but contributed to a decrease in the activity of alanine aminotransferase. Overall, our work has confirmed that HepG2 cells may serve as a useful model to obtain new data on drug effects on the metabolism of cells of hepatic origin and to assess the risk of hepatotoxicity in preclinical studies.