Vol 489, No 1 (2019)

The influence of XRCC1 protein oxidation on the modification of proteins catalyzed by poly(ADP-ribose)polymerases (PARP1 and PARP2) was studied for the first time. XRCC1, PARP1, and PARP2, functioning as scaffold proteins, are responsible for coordination of multistep repair of most abundant DNA lesions. We showed that the XRCC1 oxidation reduces the efficiency of its ADP-ribosylation and the protein affinity for poly(ADP-ribose). The ADP-ribose modification of various XRCC1 forms is enhanced in the presence of DNA polymerase β (Polβ), capable of forming a stable complex with XRCC1. Oxidation suppresses the inhibitory effect of XRCC1 and its complex with Polβ on the automodification of PARP1 and PARP2, which may enhance the efficiency of repair. The results of this study indicate that the oxidation of XRCC1 plays a role in fine regulation of poly(ADP-ribosyl)ation levels of proteins and their coordinating functions in DNA repair.

The effect of melatonin on respiration and production (release) of hydrogen peroxide during succinate oxidation in mitochondria isolated from lupine cotyledons and epicotyls of pea seedlings was studied. It was shown for the first time that melatonin (10^–7–10^–3 M) had a significant inhibitory effect on the production of peroxide by plant mitochondria, which was characterized by concentration dependence and species specificity. At the same time, melatonin (at a concentration of up to 100 μM) had virtually no effect on mitochondrial respiration rate and respiratory control coefficient. The results confirm the antioxidant function of melatonin and indicate that it is involved in the regulation of ROS levels and maintenance of redox balance in plant mitochondria.

This work is dedicated to proving our hypothesis that catecholamines and their metabolites play a crucial role in the development of retinopathy of prematurity, which leads to progressive uncontrollable vascularization in the retina, leading to blindness. The study was performed in an animal model of retinopathy of prematurity, which was achieved by hyperoxygenation in rats on postnatal days 7, 14, 21, and 30. The content of catecholamines and their metabolites in the retina of rats was determined by high performance liquid chromatography with electrochemical detection. It was shown that, in the rats with retinopathy, the content of L-DOPA on days 21 and 30 was decreased as compared to the control, whereas the content of noradrenaline on day 14 life increased compared to the control. However, we did not observe changes in the content of dopamine in the experimental animals relative to the control in any period studied. Given the published data on the involvement of catecholamines in the regulation of vasculogenesis in the retina in normal state, our data on the changes in the catecholamine metabolism in the retina in the model of retinopathy of prematurity can be regarded as evidence of the important role of catecholamines in the pathogenesis of this severe disease.

In the present work, the APX gene encoding ascorbate peroxidase in the moss Dicranum scoparium was for the first time cloned and sequenced, and a high homology of APX with ascorbate peroxidase genes of the mosses Grimmia pilifera and Physcomitrella patens was shown. The structure of the protein was characterized using bioinfomatics approach, and the activity of the enzyme under abiotic stresses was studied. An increase in the activity of ascorbate peroxidase was detected during desiccation of D. scoparium shoots. When exposed to heat shock, a decrease in the activity of ascorbate peroxidase correlated with a decrease in the expression of APX. Conserved elements, which were found in the structure of ascorbate peroxidase gene and protein, indicate that these sequences are conserved in the plant genome during evolution, in support of the importance of this enzyme in maintaining cellular redox status.

Results obtained showed that infection with HCMV prevented the death of THP-1 cells treated with DOX in both active and latent forms of infection. In the presence of mTOR inhibitors (rapamycin and Torin2), the sensitivity of the infected cells to DOX was restored. Rapamycin inhibited the expression of the HCMV protein IE1-p72 and increased sensitivity to DOX. Molecular targets for the creation of new drugs for the treatment of leukemia in patients infected with HCMV were determined.

The in vitro model of serum deprivation shows that the survival of SH-SY5Y neuronal cells is ensured by the intrinsic trophic activity of BDNF loop 4 mimetic GSB-106 (10^–7 М), which is comparable to that of endogenous neurotrophin (10^–9 М). The analysis of the cell cycle and S-phase showed that GSB-106, similarly to BDNF, induces the cell-cycle arrest in the G₁ phase, diminishes the number of cells in the S-phase, reduces the number of apoptotic cells, and does not stimulate proliferation.

The results of long-term author’s studies of the optical and complex-forming properties of more than 30 synthetic low-molecular-weight fluorophores specific for DNA are described. These studies made it possible to significantly expand the already existing database of properties of such compounds, clarify the ideas about the patterns linking the mentioned properties of fluorophores with their structure, and formulate recommendations on designing new effective DNA-specific fluorophores. The results of these studies can be used, in particular, in the development of new rapid methods for diagnosing various diseases, biotesting of probiotic and antibiotic properties of various products and wastes, etc.