Doklady Biochemistry and Biophysics最新文献

{"title":"Functional Role of Bap170 Domains in Enhancer-Dependent Gene Activity in Drosophila melanogaster.","authors":"V K Chmykhalo, D Amendola, Y V Shidlovskii, L A Lebedeva, P Schedl, E Giordano","doi":"10.1134/S1607672924601409","DOIUrl":"https://doi.org/10.1134/S1607672924601409","url":null,"abstract":"<p><p>The Bap170 subunit of the SWI/SNF chromatin remodeler exhibits activator functions when artificially recruited to the LacZ reporter promoter in enhancer-dependent transcription. In this study, the functional significance of Bap170 protein domains in reporter activation was analyzed. Deletion of the ARID domain does not reduce Bap170 activity. Increased expression of the LacZ reporter was observed in the form of Bap170 without a region that includes LXXLL motifs. Deletions of the central (RFX domain and IDRs) and C-terminal region (zinc fingers) of Bap170 lead to a significant decrease in transgene expression. Apparently, these regions of Bap170 are critical for the function of this protein in enhancer-dependent transcription.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionarily Conserved DHX9/MLE Helicase Is Involved in the Regulation of Its Own mRNA Expression Level in Drosophila melanogaster.","authors":"I A Zolin, S G Georgieva, J V Nikolenko","doi":"10.1134/S1607672924601239","DOIUrl":"https://doi.org/10.1134/S1607672924601239","url":null,"abstract":"<p><p>The MLE helicase of D. melanogaster, like its ortholog DHX9 in mammals, is involved in a wide range of processes related to the regulation of gene expression. In the present study, we investigated the impact of the mle[9] mutation on its own mRNA expression level. It was shown that in addition to the previously described deletion in the catalytic domain of the protein, which impairs its helicase activity, the mle[9] mutation contains an additional small deletion in the C-terminal domain. In the mle[9] mutation background, there was a threefold increase in the expression of the main transcript of the mle gene encoding the full-length protein. Binding of MLE to chromatin at the coding region and promoters of the mle gene and nearby enhancers was analyzed. To exclude the influence of dosage compensation, experiments were performed on females. The data obtained indicate the role of MLE in specific regulation of its own mRNA expression level in vivo at the adult stage.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GALA3-Containing Modular Nanotransporters Are Capable of Delivering Keap1 Monobody to Target Cells and Inhibiting the Formation of Reactive Oxygen Species in the Cells.","authors":"Y V Khramtsov, E S Bunin, A V Ulasov, T N Lupanova, G P Georgiev, A S Sobolev","doi":"10.1134/S1607672924601252","DOIUrl":"https://doi.org/10.1134/S1607672924601252","url":null,"abstract":"<p><p>In the previously created modular nanotransporter (MNT) capable of delivering a monobody to Keap1 into the cytosol, the endosomolytic module, translocation domain of diphtheria toxin (DTox), was replaced by the endosomolytic peptide GALA3. It was found that this substitution more than doubles the lifetime of MNT in the blood. Using confocal microscopy, it was shown that MNT with GALA3 was internalized into AML12 cells mainly due to binding to the epidermal growth factor receptor, and is also able to exit from endosomes into the cytosol. Using cellular thermal shift assay, it was shown that MNT with GALA3 and MNT with DTox are equally effective in disrupting the formation of the Nrf2 complex with Keap1, which led to similar protection of AML12 cells from the action of hydrogen peroxide. The obtained results allow not only optimizing the systemic use of MNT, but can also serve as a basis for creating agents aimed at treating diseases associated with oxidative stress.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New N⁶-Substituted Adenine Derivatives with High Antiviral Activity against RNA-Containing Viruses.","authors":"A A Zenchenko, Yu D Semenova, E R Naberezhnaya, Ya D Gumennaya, A V Lipatova, V E Oslovsky","doi":"10.1134/S1607672924600787","DOIUrl":"https://doi.org/10.1134/S1607672924600787","url":null,"abstract":"<p><p>In this work, two new compounds, N⁶-(4,5-dimethoxyphenyl)adenine and N⁶-(3,5-di-trifluoromethylphenyl)adenine, with a broad range of antiviral activity against RNA viruses were identified. We showed that these compounds exhibit pronounced antiviral activity against human poliovirus types 1, 2, and 3, belonging to enterovirus C species. Both compounds also demonstrated pronounced antiviral activity against Coxsackie viruses B3, B5, and B6, belonging to enterovirus B species. In addition, the compounds demonstrated antiviral activity against Newcastle disease virus, which belongs to the paramyxovirus genus. The compounds discovered in this work can subsequently serve as prototypes for the development of new antiviral drugs against epidemiologically significant human RNA viruses.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-molecular-weight Ligand of the Thyroid-stimulating Hormone Receptor with the Activity of a Partial Agonist and a Negative Allosteric Modulator.","authors":"K V Derkach, E A Didenko, V N Sorokoumov, I O Zakharova, A O Shpakov","doi":"10.1134/S1607672924600799","DOIUrl":"https://doi.org/10.1134/S1607672924600799","url":null,"abstract":"<p><p>Graves' disease is caused by overactivation of the thyroid-stimulating hormone receptor (TSHR). One approach for its treatment may be the use of negative allosteric modulators (NAM) of TSHR, which normalize TSHR activity and do not cause thyroid hormone (TH) deficiency. The aim of the work was to study the effect of a new compound 5-amino-4-(4-bromophenyl)-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxylic acid N-tert-butylamide (TPY4) on the basal and TSH-stimulated TH production in cultured FRTL-5 thyrocytes and on basal and thyrotropin-releasing hormone (TRH)-stimulated TH levels in the blood of rats. TPY4 stimulated TH production by thyrocytes and increased TH levels when administered intraperitoneally and orally in rats. It also decreased the TSH-stimulated TH production in thyrocytes and the TRH-stimulated TH levels in rats. Thus, TPY4 is the first known allosteric regulator of TSHR, combining the properties of NAM and a partial agonist, and can be considered as a prototype of drugs for the treatment of Graves' disease.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Method for Testing Drugs Belonging to Substrates and Inhibitors of the Transporter Protein BCRP on CACO-2 Cells.","authors":"Yu S Tranova, A A Slepnev, I V Chernykh, A V Shchulkin, P Yu Mylnikov, N M Popova, M I Povetko, E N Yakusheva","doi":"10.1134/S1607672924701266","DOIUrl":"https://doi.org/10.1134/S1607672924701266","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer resistance protein (BCRP) is an efflux membrane transporter that controls the pharmacokinetics of a large number of drugs. Its activity may change when taking some endo- and exogenous substances, thus making it a link in drug interactions.</p><p><strong>Aim: </strong>The aim of the study was to develop a methodology for testing drugs for belonging to BCRP substrates and inhibitors in vitro.</p><p><strong>Materials and methods: </strong>The work was performed on Caco-2 cells overexpressing BCRP, the cultivation was performed in a transwell system consisting of the apical and basolateral chambers. Cells were seeded at the bottom of the apical chamber, which is a semi-permeable membrane. Primarily, the transport of BCRP substrates-methotrexate, mitoxantrone, and quercetin-was evaluated in the concentration range of 1, 5, 10, and 50 μM in the direction from the basal chamber to the apical one (Papp b-a) and in the opposite direction (Papp a-b). The Papp b-a/Papp a-b ratio more than 2 characterizes the involvement of transporter proteins in the transcellular transport of substances. To confirm the involvement of BCRP in their transport, an experiment was carried out with the addition of a transporter inhibitor, reserpine, at a concentration of 50 μM to the transport medium. The concentration of substrates in the chambers was analyzed by HPLC-MS/MS.</p><p><strong>Results: </strong>After the addition of methotrexate (1 μM), mitoxantrone (1 μM), and quercetin (1-10 μM) to the apical or basolateral chambers of the transwell system, their content in the recipient chamber was not detected. At methotrexate concentration of 5 μM, the Papp b-a/Papp a-b ratio was 3.38 ± 0.08, which indicates the involvement of transporters in its transfer. When methotrexate was added to the donor chamber at concentrations of 10 and 50 μM, the Papp b-a/Papp a-b ratio decreased to values below 2. At mitoxantrone concentration of 5 μM, the Papp b-a/Papp a-b ratio was 2.72 ± 0.16. An increase in the concentration to 10 μM led to an increase in the Papp b-a/Papp a-b ratio to 6.18 ± 0.08. At the substance concentration of 50 μM, the index decreased but remained above 2. At the quercetin concentration of 50 µM, the Papp b-a/Papp ratio was below 2. Reserpine reduced the Papp b-a/Papp a-b ratio of methotrexate 3.31 times (p = 0.0002), which indicates the elimination of asymmetry in the transport of the substance. At a mitoxantrone concentration of 10 µM, reserpine reduced its Papp b-a/Papp a-b ratio 3.36 times (p < 0.0001). These results indicate the involvement of BCRP in the control of the transfer of both substances through the cellular monolayer.</p><p><strong>Conclusions: </strong>A method of testing drugs for affiliation to BCRP substrates and inhibitors using methotrexate (5 μM) and mitoxantrone (10 μM) as marker substrates and reserpine (50 μM) as inhibitor was developed and tested on Caco-2 cells.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analgesic Activity of the Low Molecular Weight Neurotrophin-3 Dipeptide Mimetic GTS-301.","authors":"L G Kolik, M A Konstantinopolsky, N M Sazonova, A D Durnev, T A Gudasheva","doi":"10.1134/S160767292460115X","DOIUrl":"https://doi.org/10.1134/S160767292460115X","url":null,"abstract":"<p><p>It was previously shown that the original dipeptide mimetic of the 4th loop of neurotrophin-3 (NT-3) hexamethylenediamide bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) (GTS-301), like the full-length neurotrophin, predominantly activates the tyrosine kinase receptor TrkC and has a neuroprotective effect in vitro at concentrations of 10^-5-10^-12 M, as well as antidiabetic (0.1 and 0.5 mg/kg) and antidepressant (5 and 10 mg/kg) effects after systemic administration in rodents. In this work, the analgesic properties of GTS-301 were identified, which were manifested in the dose range of 0.01-10 mg/kg after acute intraperitoneal injection to rats in the \"tail flick\" test. Dipeptide GTS-301 increased the threshold of pain response by 20-30%; this effect persisted for at least 24 h after administration.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascorbate Biosynthesis and Recycling Genes Are Involved in the Responses of Garlic Allium sativum L. Plants to Fusarium proliferatum Infection.","authors":"A V Shchennikova, E Z Kochieva, M A Filyushin","doi":"10.1134/S1607672924601057","DOIUrl":"https://doi.org/10.1134/S1607672924601057","url":null,"abstract":"<p><p>The expression profile of the key genes of biosynthesis (VTC2, GPP, GalDH, and GalLDH) and recycling (MDHAR1, MDHAR4, and MDHAR5) of ascorbate in response to infection with the fungal pathogen Fusarium proliferatum in garlic cultivars resistant (Podnebesny) and sensitive (Dubkovsky) to Fusarium rot was determined. It was found that differences in resistance to Fusarium lead to discrepancies in the dynamics and expression of individual genes of the ascorbate pathway, as well as in the ascorbate content. It was shown that, in response to infection, the expression level of the MDHAR4 gene increases in the resistant cultivar and decreases in the Fusarium-sensitive accession. As infection progresses, the expression levels of the VTC2 and GalLDH genes increase significantly (higher in the cv. Dubkovsky than in the cv. Podnebesny). In both cultivars, the ascorbate content increases (1.5 times higher in the cv. Dubkovsky than in the cv. Podnebesny).</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemoprotective Effect of Myrrhone against Diethylnitrosamine and Ferric Nitrile Induced Renal Cancer via Alteration of HO-1/Nrf2 and TRL4/NF-κB Signaling Pathway.","authors":"Qian Yu, Ling Tian, Jiwei Zhang","doi":"10.1134/S160767292460091X","DOIUrl":"https://doi.org/10.1134/S160767292460091X","url":null,"abstract":"<p><p>. Renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is the primary malignancy affecting the genitourinary system. It represents the majority of kidney cancer cases and is distinguished by its aggressive nature and high mortality rate. The current study investigates the chemoprotective effect of myrrhone against Diethylnitrosamine (DEN) and ferric nitrile (Fe-NTA) induced RCC in rats and elucidates the underlying mechanism.</p><p><strong>Methods: </strong>. Following a single dose of intraperitoneal DEN (200 mg/kg) and a twice-weekly administration of Fe-NTA, rats were administered either an oral dose of myrrhone (5, 10, or 15 mg/kg). The body weights and food intake of the rats were monitored at regular intervals, and the levels of renal cancer markers, antioxidants, inflammatory markers, and other parameters were assessed. Additionally, histopathological studies were conducted on the renal tissues, and the mRNA expression of Bax, Bcl-2, HO-1, SOD2, mtDNA, ATP8, PGC-1α, TRL4, and NF-κB was analyzed.</p><p><strong>Results: </strong>. The dosage-dependent administration of myrrhone demonstrated a remarkable suppression of tumor incidence and an improvement in body weight and food intake. Myrrhone markedly decreased the level of ODC, Thymidine [3H] incorporation, and renal parameters such as creatinine, uric acid, BUN, Kim-1, Cysc-C, and LDH. Additionally, myrrhone significantly altered the levels of MDA, GSH, GPx, CAT, and SOD, as well as inflammatory cytokines such as TNF-α, INF-γ, IL-1β, IL-6, and IL-10, and inflammatory parameters such as COX-2, PGE2, TGF-β1, NF-κB, and iNOS. Furthermore, myrrhone significantly decreased the histopathological score and improved the condition of histopathology. Finally, myrrhone significantly altered the mRNA expression of Bax, Bcl-2, HO-1, SOD2, mtDNA, ATP8, PGC-1α, TRL4, and NF-κB.</p><p><strong>Conclusion: </strong>: The result clearly showed the chemoprotective effect of myrrhone against diethylnitrosamine and ferric nitrile induced Renal Cancer via alteration of HO-1/Nrf2 and TRL4/NF-κB Signaling pathway.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Antitumor Activity of Low Doses of Radiation Associated with Activation of Cells' Defense System.","authors":"D V Fomina, L M Rozhdestvensky, N F Raeva, E S Vorobeva, G D Zasukhina","doi":"10.1134/S160767292470128X","DOIUrl":"https://doi.org/10.1134/S160767292470128X","url":null,"abstract":"<p><strong>Background: </strong>The effects of ionizing radiation (IR) involve a highly orchestrated series of events in cells, including DNA damage and repair, cell death, and changes in the level of proliferation associated with the stage of the cell cycle. A large number of existing studies in literature have examined the activity of genes and their regulators in mammalian cells in response to high doses of ionizing radiation. Although there are many studies, the research in effect of low doses of ionizing radiation remains limited. Though much progress has been made in understanding the basic principles of effects of low doses of radiation on individual components of biological systems, less is known about how low doses affect target molecules and regulate the cellular networks (e.g., activation of the immune system, genes and their regulators in the phenomenon of hormesis, and the formation of an adaptive response). These observations determined the purpose of the work: to investigate the activity of genes and non-coding RNAs (long non-coding RNAs and microRNAs) in various organs of mice with transplanted Lewis carcinoma after low-dose radiation.</p><p><strong>Materials and methods: </strong>Twenty-four female C57Bl/6 mice were transplanted subcutaneously with Lewis carcinoma cells (10⁵ cells in 0.2 mL of Hanks' solution). Total 4-fold X-ray irradiation with an interval of 4 days at a dose of 0.075 Gy (0.85 Gy/min) was performed on the RUST M1 from 6 days after transplantation; the tumor size was measured daily. The mice were divided into the following groups: \"Biocontrol\", \"Biocontrol + irradiation\", \"Tumor\" and \"Tumor + irradiation\". On the 19th day from the beginning of the experiment, the mice were euthanized. The expression profiles of mRNA genes, long non-coding RNAs, and microRNAs controlling the response to radiation were determined in the bone marrow, thymus, spleen, and tumor of mice.</p><p><strong>Results: </strong>Fractionated low-dose irradiation of mice with transplanted Lewis carcinoma caused a growth decrease of implanted tumor cells compared to the similar group without irradiation. At the same time, there was an activation of oncosuppressors and a decrease in the activity of oncogenes in the thymus and spleen of mice with tumor and irradiation. In the \"Tumor\" group, without irradiation, the number of activated oncogenes prevailed over the number of inactivated ones.</p><p><strong>Conclusions: </strong>Thus, the low-dose radiation exposure led to the activation of antitumor immunity in mice, which manifested itself in slowing tumor growth in animals and the induction of oncosuppressors and inhibition of oncogene expression.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}