Vol 488, No 1 (2019)

The interaction of the GAF protein with the promoters of neuron-specific genes during activation and repression of transcription was studied. We showed that, while the Su(Hw) protein remains stably associated with the promoters of these genes at different transcriptional state, the GAF protein level is significantly higher when transcription is activated.

The search for potential partners of human SELM in lysates of two cancer cell lines, HT-1080 (fibrosarcoma) and MCF-7 (breast adenocarcinoma), was carried out. Two cytoplasmic actin isoforms—cytoplasmic actin 1 (cytoskeleton β-actin) and cytoplasmic actin 2 (cytoskeletal γ-actin)—were identified as partners. In addition, the influence of two widely used antitumor selenium compounds (sodium selenite and methylseleninic acid) on the expression of SELM in cancer cells was studied. On the basis of the results obtained by real-time PCR and Western blotting, we concluded that 1 μM and 10 μM sodium selenite did not affect the expression of SELM in fibrosarcoma cells, whereas in breast adenocarcinoma cells 1 μM sodium selenite slightly increased expression and 10 μM sodium selenite significantly (approximately 2 times) decreased it. Methylseleninic acid in both cancer cell lines increased the SELM gene expression; the most pronounced effect was observed when fibrosarcoma cells were treated with 10 µM MSA (the expression of the hSelm gene increased almost 4 times).

Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor agonist–tricyclic antidepressant amitriptyline—significantly inhibits store-dependent Ca²⁺ entry, induced by endoplasmic Ca²⁺-ATPase inhibitors thapsigargin and cyclopiazonic acid, in rat peritoneal macrophages. The results suggest a possible involvement of sigma-1 receptors in the regulation of store-dependent Ca²⁺ entry in macrophages.

Selective anxiolytic fabomotizole (Afobazol®) has affinity for the Sigma-1 chaperone receptor site, quinone reductase 2 (NQO2) and MAO-A regulatory sites, and melatonin receptor type 1 (MT₁ receptor). The analysis of the effect of fabomotizole on the gene expression profile in the brain of MR (Maudsley Reactive) rats was carried out when modeling emotional stress in the open field test. A change in the expression of 14 genes was found, the results of the functional annotation of which showed that the mechanisms of action of fabomotizole may be associated with the regulation of translation of proteins (Rpl5, Rpl15, Ncl, and Ybx1), synaptic functions (Cplx2, Dlg4, Syngap1, Add1, Rab8b, Klc1, and Chn1), and cellular metabolism (Akr1d1, Bcat1, and Pkm).

It was shown for the first time that pentaamino acid derivative of fullerene C₆₀ (potassium salt of fullerenylpenta-N-dihydroxytyrosine) affects three targets of type 2 diabetes mellitus. It competitively inhibits the enzymes aldose reductase and sorbitol dehydrogenase and also has an antiglycation effect on bovine serum albumin. The inhibition constants for these enzymes were calculated.

Partial sequences of P-type ATPases were cloned from the marine microalgae Dunaliella maritima, two putative H⁺-ATPases (DmHA1 and DmHA2) and two putative Ca²⁺-ATPases (DmCA1 and DmCA2). The probable functions of the cloned proteins were suggested on the basis of their primary structure similarity with the proteins whose functions have been already characterized. The transcriptional response of the cloned D. maritima ATPase genes to a sharp increase in the NaCl concentration in the culture medium (from 100 to 500 mM) was investigated by quantitative RT-PCR. Hyperosmotic salt shock led to a significant increase in the DmHA2 expression and to a slight increase in the DmCA2 expression, whereas the expression of the two other ATPases, DmHA1 and DmCA1, was decreased. These data indicate that the DmHA2 ATPase is involved in maintenance of ion homeostasis in D. maritima cells under hyperosmotic salt shock.

Four dimeric disintegrins were isolated from the venom of the steppe viper V. ursinii using liquid chromatography. Disintegrins prevented adhesion of MCF7 cells to fibronectin, which indicates their interaction with integrin receptors of the αVβ1 type. According to mass spectrometry data, the molar masses of disintegrins are about 14 kDa. The method of peptide mapping established the structure of a new heterodimeric disintegrin weighing 13 995.5 Da and shows that it belongs to the class of RGD/KGD-containing disintegrins.

To compare the biosynthesis pathways of aromatic and isoprenoid cytokinins, a series of nucleoside derivatives of natural cytokinins was synthesized and their cytokinin activity was determined in a test system based on the model plant Arabidopsis thaliana. Cytokinin nucleosides are known to lack the hormonal activity until cleaving the ribose moiety at the position 9. Our experiments have shown that both ribo- and 5'-deoxyribo derivatives of N⁶-isopentenyladenine were able to turn into active cytokinins in planta exhibiting cytokinin activity. By contrast, 5'-deoxy nucleosides of aromatic cytokinins did not show similar activity. Since 5'-deoxy nucleosides cannot phosphorylate in vivo, the direct pathway of active cytokinin formation by cleavage of nucleotides is blocked here. The detected activity in 5'-deoxy nucleosides of isoprenoid cytokinins and the lack of the activity in 5'-deoxy nucleosides of aromatic cytokinins indicates the difference in the biosynthesis of these compounds.

A mass spectrometric method has been developed for determining the content of dopamine and serotonin derivatives, which allows evaluating the efficiency of their penetration through artificial membranes depending on the structure of their peptide fragment. In this case, the diffusion of dopamine and serotonin derivatives through the membrane occurred as a result of competitive interactions. It was shown which compounds in this mixture more easily penetrate through artificial membranes. It was found that the most promising in terms of overcoming the BBB are Boc–Pro–Srt and Boc–Pro–DOPA.