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Vol 88, No 1 (2023)

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Novel Potential Mechanisms of Regulatory B Cell-Mediated Immunosuppression

Zheremyan E.A., Ustiugova A.S., Radko A.I., Stasevich E.M., Uvarova A.N., Mitkin N.A., Kuprash D.V., Корнеев К.В.


B lymphocytes play an important role in the regulation of immune response in both normal and pathological conditions. Traditionally, the main functions of B cells were considered to be antibody production and antigen presentation, but in recent decades there have been discovered several subpopulations of regulatory B lymphocytes (Bregs) which maintain immunological tolerance and prevent overactivation of the immune system. Memory (mBregs, CD19+CD24hiCD27+) and transitional (tBregs, CD19+CD24hiCD38hi) subpopulations of Bregs are usually considered in the context of studying the role of these B cells in various human pathologies. However, the mechanisms by which these Breg subpopulations exert their immunosuppressive activity remain poorly understood. In this work, we used bioinformatic analysis of open-source RNA sequencing data to propose potential mechanisms of B cell immunosuppression. Analysis of differential gene expression before and after activation of these subpopulations allowed us to identify six candidate molecules that may determine the functionality of mBregs and tBregs. IL4I1-, SIRPA-, and SLAMF7-dependent mechanisms of immunosuppression may be characteristic of both Breg subsets, while NID1-, CST7-, and ADORA2B-dependent mechanisms may be predominantly characteristic of tBregs. An in-depth understanding of the molecular mechanisms of anti-inflammatory immune response of B lymphocytes is an important task for both basic science and applied medicine and can facilitate the introduction of new approaches to the therapy of complex diseases.

Biohimiâ. 2023;88(1):3-13
pages 3-13 views

Epithelial-Mesenchymal Transition of Breast Cancer Cells Activated by SNAIL1 Transcription Factor

Litovka N.I., Zhitnyak I.Y., Gloushankova N.A.


Cancer cells use the program of epithelial-mesenchymal transition for initiation of the invasion-metastasis cascade. Using confocal and video-microscopy, in breast cancer MCF-7 cells undergoing Snail1-induced epithelial-mesenchymal transition reorganization of cytoskeleton was studied. We used the line of MCF-7 cells stably expressing tetOff SNAI1 construct (MCF-7-SNAI1 cells). After tetracycline washing and Snail1 activation MCF-7-SNAI1 cells underwent EMT and acquired a migratory phenotype retaining expression of E-cadherin. We identified five variants of the mesenchymal phenotype, differing in cell morphology and migration rate. Migrating cells had high degree of plasticity which allowed them to quickly change both the phenotype and the speed of movement. The changes of phenotype of MCF-7-SNAI1 cells are based on Arp2/3-mediated branched actin polymerization in lamellipodia, myosin-based contractility in the zone behind the nucleus, redistribution of adhesive proteins from cell-cell contacts to the leading edge and reorganization of intermediate keratin filaments.

Biohimiâ. 2023;88(1):14-28
pages 14-28 views

Encapsulins: Structure, Properties, Application in Biotechnology (Review)

Chmelyuk N.S., Oda V.V., Gabashvili A.N., Abakumov M.A.


In 1994 a new class of prokaryotic compartments was discovered, collectively called “encapsulins” or “nanocompartments”. Encapsulin shell protomer proteins self-assemble to form icosahedral structures of various diameters (24-42 nm). Inside of nanocompartments shells, one or several cargo proteins, diverse in their functions, can be encapsulated. In addition, non-native cargo proteins can be loaded into nanocompartments, and shell surfaces can be modified via various compounds, which makes it possible to create targeted drug delivery systems, labels for optical and MRI imaging, and to use encapsulins as bioreactors. This review describes a number of approaches to the application of encapsulins in various fields of science, including biomedicine and nanobiotechnologies.

Biohimiâ. 2023;88(1):29-46
pages 29-46 views

Therapy Induced Tumor Cell Senescence: Mechanisms and Ways to Overcome (Review)

Zamkova M.A., Persyantseva N.A., Tatarskiy V.V.


The plasticity of tumor cells due to the multiplicity of molecular regulation allows to evade the cytocidal effects of chemo- and/or radiation therapy. Metabolic adaptation of survived cells is based on transcriptional reprogramming. Because of the similarities with the natural cell aging, specific features of survived tumor cells comprise the phenotype of therapy induced senescence. Most importantly, the senescent cells differ from the parental since they become less responsive to drugs and form the aggressive progeny. The importance of the problem is explained by general biological significance of transcriptional reprogramming as a mechanism of adaptation to stress, and by the emerging perspective of its pharmacological targeting. We analyze the mechanisms of regulation of therapy induced tumor cell senescence, as well as the new drug combinations to prevent this clinically unfavorable phenomenon.

Biohimiâ. 2023;88(1):47-67
pages 47-67 views

Influence of the Structure of the Coat Protein N-Terminal Segment in Potato Virus X and Alternanthera Mosaic Virus on the Structure and Physico-Chemical Properties of Virions

Ksenofontov L.A., Petoukhov M.V., Matveev V.V., Fedorova N.V., Semenyuk P.I., Arutyunyan A.M., Manukhova T.I., Evtushenko E.A., Nikitin N.A., Karpova O.V., Shtykova E.V.


The amino acid sequences of coat proteins (CPs) of potexviruses such as potato virus X (PVX) and alternanthera mosaic virus (AltMV) share about 40% sequence identity. However, the N-terminal CP domains of these virions differ both in length (the N-terminal CP domain of PVX is longer by 28 residues, ∆N = 28), and in amino acid sequence. In this work, we determined the effect of the N-terminal CP domain on the structure and physicochemical properties of the entire PVX and AltMV virions. It was shown that the melting point of PVX samples is 10-12°C higher than that of AltMV preparations; the circular dichroism spectra of these viruses also differ significantly. Spatial alignment of the existing high-resolution potexvirus CP structures showed that the RMSD value between Cα-atoms was the largest for the N-terminal domains of the two compared models. From computer simulations the ∆N-terminal CP domain of PVX is completely disordered. According to synchrotron small-angle X-ray scattering (SAXS) data, the structure of CP of PVX and AltMV virions differs, in particular, CP PVX has a larger size of crystallinity regions and, therefore, is more ordered. Using SAXS, virion diameters and helix parameters in solution are calculated. The influence of the conformation and localization of the N-terminal domain of PVX CP relative to the surface of the virion on its structure was revealed. Presumably, the increased thermal stability of PVX virions compared to AltMV is provided by the elongated N-terminal domains (ΔN = 28), which ensures additional contact between the adjacent CP subunits in the PVX virion.

Biohimiâ. 2023;88(1):68-82
pages 68-82 views

Effect of Chemical Chaperones on Processes of Protein Aggregation Proceeding in Different Kinetic Regimes

Mikhaylova V.V., Eronina T.B., Chebotareva N.A., Kurganov B.I.


The formation and accumulation of protein aggregates adversely affect intracellular processes in a living cell and are a negative factor in the production and storage of protein preparations. Chemical chaperones can prevent protein aggregation, but this property is not universal and depends on the structure of the target protein and the kinetics of its aggregation. In this work, we studied the effect of betaine (Bet) and lysine (Lys) on test systems based on thermal aggregation of muscle glycogen phosphorylase b (Phb) at 48°C, UV-irradiated Phb (UV-Phb) at 37°C and apo-form of Phb (apo-Phb) at 37°C and characterized by the order of aggregation with respect to the protein (n) equal to 0.5, 1 or 2, respectively. Dynamic light scattering, differential scanning calorimetry, and analytical ultracentrifugation have shown that Bet protects Phb and apo-Phb from aggregation, but accelerates the aggregation of UV-Phb. At the same time, Lys prevents UV-Phb and apo-Phb aggregation, but increases the rate of Phb aggregate formation. The mechanisms of chemical chaperone action on the tertiary and quaternary structures and the kinetics of thermal aggregation of the target proteins are discussed. Comparison of the effect of chemical chaperones on test systems with different kinetic regimes of aggregation provides more complete information about the mechanism of their action.

Biohimiâ. 2023;88(1):83-96
pages 83-96 views

Inhibitors of Galactonolactone Oxidase From Trypanosoma cruzi Based on Allylpolyalkoxybenzenes

Chudin A.A., Zlotnikov I.D., Krylov S.S., Semenov V.V., Kudryashova E.V.


Inhibition of the biosynthetic pathways of compounds essential for T. cruzi is considered by researchers as one of the possible mechanisms of action of potential drugs against Chagas disease. As one of these mechanisms, we consider inhibition of galactonolactone oxidase from T. cruzi (TcGAL), which catalyzes the final step in the synthesis of vitamin C, an antioxidant that T. cruzi is unable to assimilate from outside and must synthesize itself. In this work, for the first time, a class of effective inhibitors of TcGAL was found - allylbenzenes from plant sources. A non-competitive mechanism of action of apiol has been established and it has been found that natural allylpolyalkoxybenzenes (APAB) - apiol, dillapiol, etc. are effective inhibitors of TcGAL with IC50 = 20-130 µM. It was found that the conjugation of APAB with triphenylphosphonium, which ensures the selective delivery of biologically active substances to mitochondria, makes it possible to increase the efficiency and/or the maximum percentage of inhibition compared to unmodified APAB.

Biohimiâ. 2023;88(1):97-109
pages 97-109 views

Melatonin Can Enhance the Effect of Drugs Used in the Treatment of Leukemia

Lomovskiy A.I., Baburina Y.L., Fadeev R.S., Lomovskaya Y.V., Kobyakova M.I., Krestinin R.R., Sotnikova L.D., Krestinina O.V.


Melatonin (N-acetyl-5-methoxytryptamine, MEL), secreted by the pineal gland, plays an important role in the regulation of the different functions in human. However, there are the facts that MEL has an antitumor effect in various types of cancer. We have studied the combined effect of MEL and targeted drugs such as cytarabine (CYT) and navitoclax (ABT-737) on the development of acute myeloid leukemia in the MV4-11 cell model. The combined action of MEL with CYT or ABT-737 contributed to a decrease in the proliferative activity of leukemia cells, a drop in the membrane potential of mitochondria, and an increase in the production of reactive oxygen species and cytosolic Ca2+. We have shown that MEL, together with CYT or ABT-737, increases expression of homologous C/EBP protein and autophagy marker LC3A/B and decreases protein disulfide isomerase and immunoglobulin-binding protein levels, and consequently modulate endoplasmic stress. reticulum and initiate autophagy. The obtained data support the earlier suggestion that MEL may have potential benefits in cancer treatment and may be considered as an additive to drugs used in therapy.

Biohimiâ. 2023;88(1):110-124
pages 110-124 views

The Effect of Deletions of Genes Encoding Pho3p and Bgl2p on the Polyphosphate Level, Stress Adaptation and Attachment of These Proteins in Saccharomyces cerevisiae Cell Wall

Kalebina T.S., Kulakovskaya E.V., Rekstina V.V., Trilisenko L.V., Ziganshin R.H., Marmiy N.V., Esipov D.S., Kulakovskaya T.V.


Inorganic polyphosphates (polyP), according to literature data, are involved in the regulatory processes of molecular complex of the Saccharomyces cerevisiae cell wall (CW). The aim of the work was to reveal relationship between polyP, acid phosphatase Pho3p, and the major CW protein, glucanosyl transglycosylase Bgl2p, which is the main glucan-remodelling enzyme with amyloid properties. It has been shown that the yeast cells with deletion of the PHO3 gene contain more high molecular alkali-soluble polyP and are also more resistant to exposure to alkali and manganese ions compared to the wild type strain. This suggests that Pho3p is responsible for hydrolysis of the high molecular polyP on the surface of yeast cells, and these polyP belong to the stress resistance factors. The S. cerevisiae strain with deletion of the BGL2 gene is similar to the Δpho3 strain both in the level of high molecular alkali-soluble polyP and in the increased resistance to alkali and manganese. Comparative analysis of the CW proteins demonstrated correlation between the extractability of the acid phosphatase and Bgl2p, and also revealed a change in the mode of Bgl2p attachment to the CW of the strain lacking Pho3p. It has been suggested that Bgl2p and Pho3p are able to form a metabolon or its parts that connects biogenesis of the main structural polymer of the CW, glucan, and catabolism of an important regulatory polymer, polyphosphates.

Biohimiâ. 2023;88(1):125-135
pages 125-135 views

Non-Specific Porins From the Outer Membrane of Yersinia pseudotuberculosis Effect on Mice Brain Cortex Tissues

Portnyagina O.Y., Ivashkevich D.N., Duizen I.V., Shevchenko L.S., Novikova O.D.


It was found that with a single immunization of OmpF and OmpC mice with Yersinia pseudotuberculosis porins, against the background of an increasing titer of specific antibodies, pathological changes develop in the deep layers of the cerebral cortex, characterized by dystrophic changes in cells. At the same time, an increased level of caspase 3 expression is observed in neurons, which indicates the induction of proapoptotic signaling pathways. The results obtained indicate the potential ability of nonspecific pore-forming proteins of the outer membrane of Gram-negative bacteria to initiate the development of degenerative changes in brain cells.

Biohimiâ. 2023;88(1):136-146
pages 136-146 views

Acylation of the Rat Brain Proteins is Affected by the Inhibition of Pyruvate Dehydrogenase in vivo

Aleshin V.A., Sibiryakina D.A., Kazantsev A.V., Graf A.V., Bunik V.I.


Organism adaptation to metabolic challenges requires coupling of metabolism to gene expression. In this regard, acylations of histones and metabolic proteins acquire significant interest. We hypothesize that adaptive response to inhibition of a key metabolic process, catalyzed by the acetyl-CoA-generating pyruvate dehydrogenase (PDH) complex, is mediated by changes in the protein acylations. The hypothesis is tested by intranasal administration to animals of PDH-specific inhibitors acetyl(methyl)phosphinate (AcMeP) or acetylphosphonate methyl ester (AcPMe), followed by the assessment of physiological parameters, brain protein acylation, and expression/phosphorylation of PDHA subunit. At the same dose, AcMeP, but not AcPMe, decreases acetylation and increases succinylation of the brain proteins with apparent molecular masses of 15-20 kDa. Regarding the proteins of 30-50 kDa, a strong inhibitor AcMeP affects acetylation only, while a less efficient AcPMe mostly increases succinylation. The unchanged succinylation of the 30-50 kDa proteins after the administration of AcMeP coincides with the upregulation of desuccinylase SIRT5. No significant differences between the levels of brain PDHA expression, PDHA phosphorylation, parameters of behavior or ECG are observed in the studied animal groups. The data indicate that the short-term inhibition of brain PDH affects acetylation and/or succinylation of the brain proteins, that depends on the inhibitor potency, protein molecular mass, and acylation type. The homeostatic nature of these changes is implied by the stability of physiological parameters after the PDH inhibition.

Biohimiâ. 2023;88(1):147-163
pages 147-163 views

On the Paper by Leonid A. Gavrilov and Natalia S. Gavrilova entitled “Trends in Human Species-Specific Lifespan and Actuarial Aging Rate” Published in Biokhimiya, Vol. 87, N. 12, pp. 1998-2011

Mihalskiy A.I.



Biohimiâ. 2023;88(1):164-165
pages 164-165 views

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