O A Buneeva, I G Kapitsa, M G Zavyalova, S A Kaloshina, V G Zgoda, A E Medvedev
{"title":"The delayed effect of the neuroprotector fabomotizole on the brain proteome in rats with the rotenone model of parkinsonism.","authors":"O A Buneeva, I G Kapitsa, M G Zavyalova, S A Kaloshina, V G Zgoda, A E Medvedev","doi":"10.18097/PBMCR1586","DOIUrl":"https://doi.org/10.18097/PBMCR1586","url":null,"abstract":"<p><p>Fabomotizole is an original anxiolytic agent developed at the Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies that acts on a number of important receptor systems of the brain. In a model of Parkinson's disease induced in rats by a course of rotenone administration, fabomotizole attenuated manifestations of behavioral impairments and influenced the profile and relative content of brain proteins. Five days after the last administration of rotenone, the fabomotizole effect on the behavioral reactions of rats persisted. According to the proteomic study, the profile of brain proteins and changes in their relative content differed significantly from the results obtained immediately after the last administration of rotenone, as well as rotenone in combination with fabomotizole. Changes in the relative content of almost all proteins detected immediately after the last administration of rotenone or rotenone with fabomotizole were not detectable five days later. However, at this time point, there were changes in the relative content of other proteins associated with neurodegeneration in Parkinson's and Alzheimer's diseases. Such dynamics suggests a wave-like change in the content of pathogenetically important brain proteins involved in the mechanisms of neurodegeneration and neuroprotection.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 3","pages":"217-226"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Selection of optimal protein sets as serological tumor marker signatures.","authors":"S N Naryzhny, O K Legina","doi":"10.18097/PBMCR1552","DOIUrl":"https://doi.org/10.18097/PBMCR1552","url":null,"abstract":"<p><p>Currently, various potential tumor markers have been proposed for clinical practice. Although some of them are successfully used in diagnostics, and treatment, none of them fully meets the needs of oncology. Therefore, the search for new markers continues. In this context much attention is paid to multiomics technologies such as genomics, transcriptomics, and metabolomics. However, since tumor biomarkers are mainly proteins, proteomics plays a central role in the search of tumor markers. Blood is the most popular source of information about a patient's health and therefore the search is focused on plasma/serum proteins In order to increase the sensitivity and specificity of the analysis, a very promising approach is to assess the levels of certain sets of relevant proteins rather than individual proteins and this review is devoted to analysis of this problem.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 3","pages":"163-194"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M I Airapetov, S O Eresko, A A Shchukina, N M Matveev, M A Andreev, E R Bychkov, A A Lebedev, P D Shabanov
{"title":"The study of the azithromycin effect on gene expression of the toll-like receptor system in the brain nucleus accumbens of rats during ethanol withdrawal and search for possible molecular targets by an in silico method.","authors":"M I Airapetov, S O Eresko, A A Shchukina, N M Matveev, M A Andreev, E R Bychkov, A A Lebedev, P D Shabanov","doi":"10.18097/PBMCR1523","DOIUrl":"https://doi.org/10.18097/PBMCR1523","url":null,"abstract":"<p><p>The brain's nucleus accumbens (NAc) is a key link in the internal reinforcement system, which mediates manifestations of various components of addiction, including ethanol. The neuroinflammatory theory of alcoholism development suggests that changes in the molecular mechanisms of the innate immune system may be involved in the development of this pathology. The aim of our study was to investigate the effect of azithromycin (AZM) on expression of toll-like receptor system genes in the NAc during experimental alcoholization of rats. The objectives of the study also included an in silico search for possible molecular targets for AZM that could be associated with the toll-like receptor system. AZM corrected the changes observed in the expression of toll-like receptor system genes under conditions of alcohol withdrawal after long-term ethanol exposure in the NAc of the brain. The in silico analysis revealed the most probable proteins which could be involved in the interaction with AZM. Based on results of these predictions a number of assumptions about possible ways of implementing the observed pharmacological effect of AZM in the experiment have been made.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"95-102"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Slow-binding inhibitors of enzymes: kinetic characteristics and pharmacological interest.","authors":"Z M Shaihutdinova, T N Pashirova, P Masson","doi":"10.18097/PBMCR1536","DOIUrl":"https://doi.org/10.18097/PBMCR1536","url":null,"abstract":"<p><p>Currently, the search for new slow-binding inhibitors of enzymes (SBI) and their identification primary in vitro studies still attracts much attention in the context of their potential role as putative pharmacological agents for the treatment of various diseases. In contrast to their classical reversible analogues, SBI exhibit a slow enzyme binding kinetics, where the equilibrium steady-state is reached not in microseconds, but after longer time intervals. Such compounds could be promising drugs, because regardless of their pharmacokinetics in the bloodstream, they have such advantages as high affinity for the target enzyme, long residence time on the target, and therefore, prolonged action. These pharmacological properties ensure optimized dosage of drugs required to achieve high activity with less side effects. In this review we have considered mechanisms of SBI interaction with enzyme targets, the principles of their recognition at the level of in vitro studies and analysis of binding and kinetic parameters.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"81-94"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A V Kachanov, S A Brezgin, N I Ponomareva, A N Lukashev, V P Chulanov, D S Kostyushev, A P Kostyusheva
{"title":"The m6A methylation system limits hepatitis B virus replication.","authors":"A V Kachanov, S A Brezgin, N I Ponomareva, A N Lukashev, V P Chulanov, D S Kostyushev, A P Kostyusheva","doi":"10.18097/PBMCR1509","DOIUrl":"https://doi.org/10.18097/PBMCR1509","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) is a common RNA modification, which plays a critical role in RNA fate and regulating such aspects as splicing, stability, nuclear export, and translation efficiency. The introduction, removal, and recognition of m6A modifications in RNA are regulated by a number of factors, known as writer, eraser, and reader proteins. It is known that the m6A modification can play an important role in the life cycle of viruses, including hepatitis B virus. The m6A methylation system has a significant impact on the hepatitis B viral cycle (HBV), particularly, on stability of mRNA transcripts, encapsidation efficiency, and reverse transcription of HBV pgRNA. In this study, we assessed the effect of knockout and activation of expression of several factors of the m6A methylation system on the HBV viral cycle, including pregenomic RNA (pgRNA) and circular covalently closed DNA (cccDNA). The study was carried out using the StCas9 nuclease system for knockout and the dCas9-p300 system for activation of gene expression. The levels of pgRNA and cccDNA were estimated by real-time PCR. The data obtained show the restriction of the viral cycle at the basal level by the factors METTL3, METTL14, METTL16, FTO, JMJD6, and hnRNPA2B1, as well as suppression of the viral cycle with overexpression of all of the above factors, except for hnRNPA2B1.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"127-136"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iu S Kisrieva, N F Samenkova, N A Bolochenkov, A L Rusanov, D D Romashin, N A Solovyeva, I I Karuzina, A V Lisitsa, N A Petushkova
{"title":"Changes in cell motility proteins profile in HaCaT keratinocytes response to UVA exposure.","authors":"Iu S Kisrieva, N F Samenkova, N A Bolochenkov, A L Rusanov, D D Romashin, N A Solovyeva, I I Karuzina, A V Lisitsa, N A Petushkova","doi":"10.18097/PBMCR1482","DOIUrl":"10.18097/PBMCR1482","url":null,"abstract":"<p><p>A comparative analysis of HaCaT keratinocyte proteins has been performed after cell exposure to subtoxic doses (5 J/cm² and 25 J/cm²) of ultraviolet A (UVA) radiation. 930 proteins were identified by two or more unique peptides. More than half of all identified proteins (54.5%) demonstrated at least 2-fold increase in their relative content after HaCaT keratinocyte irradiation with a cumulative dose of 5 J/cm², while a decrease in the relative content was found only for 4 proteins. Irradiation of keratinocytes with a cumulative dose of 25 J/cm² resulted in a decrease in the proportion of up-regulated proteins (43.0%) and an increase in the number of down-regulated proteins (84). Among the proteins with increased relative content in HaCaT keratinocytes the most proteins were associated with \"cell motility\" (GO: 0048870), as well as regulation of cell shape and size, cell morphogenesis, and skin remodeling.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"146-157"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O A Buneeva, V I Fedchenko, S A Kaloshina, M G Zavyalova, V G Zgoda, A E Medvedev
{"title":"Interaction of kidney proteins of normal and hypertensive rats with fragments of renalase peptide RP220.","authors":"O A Buneeva, V I Fedchenko, S A Kaloshina, M G Zavyalova, V G Zgoda, A E Medvedev","doi":"10.18097/PBMCR1567","DOIUrl":"https://doi.org/10.18097/PBMCR1567","url":null,"abstract":"<p><p>Renalase (RNLS) is a protein involved in the regulation of blood pressure; it has various functions inside and outside cells. The twenty-membered peptide RP220, corresponding to the amino acid sequence of human RNLS 220-239, reproduces a number of effects of extracellular RNLS and can bind to many intracellular proteins in the kidney. The RP220 sequence contains several cleavage sites for extracellular proteases, which could potentially produce RP224-232 and RP233-239 peptides. The aim of this work was to perform proteomic profiling of kidney tissue from normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) derived from WKY, using potential proteolytic fragments (RP224-232 and RP233-239) of the RP220 peptide as affinity ligands, and to compare these proteomic profiles with the profiles obtained using the parent RP220 peptide. The obtained results indicate that the relative content of proteins bound to the RNLS peptides in SHR, compared to that in WKY rats, changes most significantly in the case of the RP224-232 peptide. Almost all of these proteins, with a few exceptions, are associated with cardiovascular pathology, many with hypertension. The results of our work indicate that proteolytic processing of RP220 does not lead to the inactivation of this peptide, but to a change in its ligand/regulatory properties, as well as the repertoire of potential protein partners and, consequently, protein-protein interactions that may have possible pharmacological application.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"103-115"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E V Iurova, E V Rastorgueva, E A Beloborodov, D E Sugak, E S Pogodina, A N Fomin, Y V Saenko
{"title":"Peptide toxins targeting ion channels as cytoprotective agents in ischemia-reperfusion injury of epithelial cells.","authors":"E V Iurova, E V Rastorgueva, E A Beloborodov, D E Sugak, E S Pogodina, A N Fomin, Y V Saenko","doi":"10.18097/PBMCR1553","DOIUrl":"https://doi.org/10.18097/PBMCR1553","url":null,"abstract":"<p><p>Ischemia-reperfusion injury (IRI) is a complex process accompanying cessation of blood supply to an organ or tissue followed by subsequent restoration of blood circulation. The IRI is especially prominent in surgery and organ transplantation. One of the strategies for reducing organ and tissue damage during transplantation is regulation of intracellular ion concentrations. Maintenance of ion concentrations in the cell during damage development can be controlled by influencing voltage-dependent ion channels with certain types of compounds. We propose the peptide toxins tropic to calcium (omega-hexatoxin-Hv1a) and sodium (mu-agatoxin-Aa1a) voltage-dependent ion channels as potential agents reducing IRI. The toxins were obtained using solid-phase peptide synthesis. The IRI modeling for evaluation of the action of toxins was carried out on a culture of epithelial cells CHO-K1 during their incubation under conditions of hypoxia and nutrient deprivation followed by subsequent replenishment of the nutrient medium. The level of cell death, concentrations of calcium, sodium, potassium ions, and pH were recorded using a multimodal plate reader and fluorescent dyes. Experiments have shown that regardless of different mechanisms of action, both toxins reduced the development of CHO-K1 cell death by changing ion concentrations and maintaining the pH level.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"116-126"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The P2X3 receptor blocker AF-353 (Ro-4) reduces bioenergetic index of a primary mixed culture of hippocampal neurons.","authors":"A S Zelentsova, M Yu Skorkina, A V Deykin","doi":"10.18097/PBMCR1531","DOIUrl":"https://doi.org/10.18097/PBMCR1531","url":null,"abstract":"<p><p>In clinical studies, the purinergic receptor P2X3 is considered as a molecular target for pain correction in spinal sensory neurons by highly selective antagonists based on diaminopyrimidine derivatives. In the CNS, P2X3 receptors are involved in synaptic plasticity underlying memory and learning. Currently, potent and selective allosteric modulators of P2X3 and P2X2/3 receptors have been recognized among diaminopyrimidine derivatives. These include 5-(5-iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine (Ro-4 or AF-353), gefapixant, which have a good pharmacokinetic profile and are less active with respect to a wide range of kinases, receptors, and ion channels. Although the therapeutic value of P2X3 receptor blockade in CNS neurons has not been studied, however, certain evidence exists in the literature that this receptor could represent a new target in the search for antiepileptic drugs, as well as drugs that reduce anxiety and stress. The aim of the work was to study the effect of the P2X3 receptor antagonist AF-353 (Ro-4) on the neuronal bioenergetic health index (BHI) in a primary mixed hippocampal culture. The P2X3 receptor blockade in embryonic and postnatal mouse hippocampal neuron cultures increased non-mitochondrial respiration by 27.5% and 15.8%, respectively, proton loss by 31.0% and 61.4%, and decreased basal respiration by 89% and 39% compared to the control. The neuronal BHI decrease in the postnatal culture was 68% compared to the control. The obtained results indicate the effect of AF-353 on mitochondrial respiration of a primary mixed culture of hippocampal neurons; this reveals the potential of the P2X3 receptor as a pharmacological target in hypoxic conditions of the brain.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 2","pages":"137-145"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O A Buneeva, V I Fedchenko, O V Gnedenko, S A Kaloshina, M V Medvedeva, M G Zavyalova, A S Ivanov, V G Zgoda, A E Medvedev
{"title":"Interaction of rat kidney proteins with the renalase peptide RP220 and its potential proteolytic fragment RP224-232: a comparative proteomic analysis.","authors":"O A Buneeva, V I Fedchenko, O V Gnedenko, S A Kaloshina, M V Medvedeva, M G Zavyalova, A S Ivanov, V G Zgoda, A E Medvedev","doi":"10.18097/PBMCR1559","DOIUrl":"10.18097/PBMCR1559","url":null,"abstract":"<p><p>Renalase (RNLS) is a protein playing different roles inside and outside cells. A 20-mer synthetic peptide corresponding to the human RNLS amino acid sequence 220-239 (RP220) exhibits a number of pharmacologically attractive activities in vitro and in vivo and can bind to many renal intracellular proteins. The RP220 sequence contains several cleavage sites for extracellular and circulating proteases. Here, we investigated the interaction of model proteins with the renalase peptide RP220 and a synthetic peptide corresponding to the amino acid sequence of RNLS 224-232, named RP224-232. We also performed affinity-based proteomic profiling of normotensive rat kidney samples with these peptides as affinity ligands. The obtained results indicate that both peptides exhibit almost the same affinity for model proteins (pyruvate kinase and lactate dehydrogenase), and the kidney proteomic profiles differ slightly. At the same time, the relative content of a number of kidney proteins bound to the RP224-232 peptide was even higher than in the case of using RP220. This suggests that proteolytic processing of RP220 does not inactivate this peptide; moreover, it could contribute to the formation of shorter peptides with additional pharmacological activities.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"71 1","pages":"65-70"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}