K I Mosalev, I D Ivanov, M V Tenditnik, E E Shults, V A Vavilin
{"title":"Hepatotropic activity of a betulonic acid based compound.","authors":"K I Mosalev, I D Ivanov, M V Tenditnik, E E Shults, V A Vavilin","doi":"10.18097/PBMC20247001015","DOIUrl":"10.18097/PBMC20247001015","url":null,"abstract":"<p><p>Using the model of cyclophosphamide (CP)-induced immunosuppression in C57BL/6 mice, the hepatotropic effects of a conjugate of betulonic acid with 9-(4-methylpiperazin-1-ylmethyl)-2-(1,2,3-triazolyl) oreozelone (BABC) have been studied. In the liver of treated animals the expression of genes for cytochromes (CYP 1A1, CYP 1A2, CYP 3A44, CYP 2B10, CYP 2C29, CYP 17A1), PPARA, and cytokines (TNF-α, IL-1β, IL-12α, IL-10) and the relative levels of NF-κB p65, GST-π, and NAT-1 proteins were determined. On day six after administration of the compound and CP to animals a significant (3.2-fold) increase in the expression of the CYP 2B10 as compared to the control group was observed. Treatment of mice with the compound and CP also caused a 2.4-fold increase in the mRNA level of the pro-inflammatory TNF-α gene as compared to the group of animals receiving CP. Administration of the studied compound to intact animals was accompanied by a 2.5-fold increase in the IL-1β expression and a 1.8-fold decrease in the IL-10 expression as compared to the control group. An increase in the expression of pro-inflammatory cytokine genes in the liver of animals treated with the compound was accompanied by an increase in the content of NF-κB p65 (by 1.6 times), as well as an increase in the relative amount of NAT-1 protein (by 2.7 times) as compared to control animals.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 1","pages":"15-24"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048672","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 Chernyshova, D V Potanina, I S Sadovnikova, E P Krutskikh, D E Volodina, N A Samoylova, A P Gureev
{"title":"The study of the protective effect of mitochondrial uncouplers during acute toxicity of the fungicide difenoconazole in different organs of mice.","authors":"E V Chernyshova, D V Potanina, I S Sadovnikova, E P Krutskikh, D E Volodina, N A Samoylova, A P Gureev","doi":"10.18097/PBMC20247001041","DOIUrl":"10.18097/PBMC20247001041","url":null,"abstract":"<p><p>Pesticides represent a serious problem for agricultural workers due to their neurotoxic effects. The aim of this study was to evaluate the ability of pharmacological oxidative phosphorylation uncouplers to reduce the effect of the difenoconazole fungicide on mitochondrial DNA (mtDNA) of various organs in mice. Injections of difenoconazole caused cognitive deficits in mice, and the protonophore 2,4-dinitrophenol (2,4-DNP) and Azur I (AzI), a demethylated metabolite of methylene blue (MB), prevented the deterioration of cognitive abilities in mice induced by difenoconazole. Difenoconazole increased the rate of reactive oxygen species (ROS) production, likely through inhibition of complex I of the mitochondrial respiratory chain. After intraperitoneal administration of difenoconazole lungs, testes and midbrain were most sensitive to the accumulation of mtDNA damage. In contrast, the cerebral cortex and hippocampus were not tolerant to the effects of difenoconazole. The protonophore 2,4-DNP reduced the rate of ROS formation and significantly reduced the amount of mtDNA damage caused by difenoconazole in the midbrain, and partially, in the lungs and testes. MB, an alternative electron carrier capable of bypassing inhibited complex I, had no effect on the effect of difenoconazole on mtDNA, while its metabolite AzI, a demethylated metabolite of MB, was able to protect the mtDNA of the midbrain and testes. Thus, mitochondria-targeted therapy is a promising approach to reduce pesticide toxicity for agricultural workers.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 1","pages":"41-51"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048676","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}
D B Chudakov, O A Shustova, O D Kotsareva, A A Generalov, M S Streltsova, Yu D Vavilova, G V Fattakhova
{"title":"Chemical chaperone TUDCA selectively inhibits production of allergen-specific IgE in a low-dose model of allergy.","authors":"D B Chudakov, O A Shustova, O D Kotsareva, A A Generalov, M S Streltsova, Yu D Vavilova, G V Fattakhova","doi":"10.18097/PBMC20247001005","DOIUrl":"10.18097/PBMC20247001005","url":null,"abstract":"<p><p>The cellular response to endoplasmic reticulum (ER) stress accompanies plasma cell maturation and is one of triggers and cofactors of the local inflammatory response. Chemical chaperones, low-molecular substances that eliminate pathological ER stress, are proposed as means of treating pathologies associated with ER stress. The aim of this study was to evaluate the effect and mechanisms of influence of chemical chaperones on the humoral response in a low-dose model of allergy. The allergic immune response was induced in BALB/c mice by repeated administration of ovalbumin at a dose of 100 ng for 6 weeks. Some animals were injected with both the antigen and the chemical chaperones, TUDCA (tauroursodeoxycholic acid) or 4-PBA (4-phenylbutyrate). Administration of TUDCA, but not 4-PBA, suppressed production of allergen-specific IgE (a 2.5-fold decrease in titer). None of the chemical chaperones affected the production of specific IgG1. The effect of TUDCA was associated with suppression of the switch to IgE synthesis in regional lymph nodes. This phenomenon was associated with suppressed expression of genes encoding cytokines involved in type 2 immune response, especially Il4 and Il9, which in turn could be caused by suppression of IL-33 release. In addition, TUDCA significantly suppressed expression of the cytokine APRIL, and to a lesser extent, BAFF. Thus, TUDCA inhibition of the allergy-specific IgE production is due to suppression of the release of IL-33 and a decrease in the production of type 2 immune response cytokines, as well as suppression of the expression of the cytokines APRIL and BAFF.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 1","pages":"5-14"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048670","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}
T S Kalinina, V V Kononchuk, I S Valembakhov, V O Pustylnyak, V V Kozlov, L F Gulyaeva
{"title":"Expression of AhR-regulated miRNAs in non-small cell lung cancer in smokers and never smokers.","authors":"T S Kalinina, V V Kononchuk, I S Valembakhov, V O Pustylnyak, V V Kozlov, L F Gulyaeva","doi":"10.18097/PBMC20247001052","DOIUrl":"10.18097/PBMC20247001052","url":null,"abstract":"<p><p>Smoking is a risk factor for non-small cell lung cancer (NSCLC). The most common subtypes of NSCLC are lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC). The cigarette smoke contains aryl hydrocarbon receptor (AhR) ligands, such as benzo(a)pyrene (BaP). By activating the AhR, BaP can change the expression of many genes, including miRNA-encoding genes. In this study, we have evaluated the expression of few miRNAs potentially regulated by AhR (miR-21, -342, -93, -181a, -146a), as well as CYP1A1, a known AhR target gene, in lung tumor samples from smoking (n=40) and non-smoking (n=30) patients with LAC and from smoking patients with SCC (n=40). We have also collected macroscopically normal lung tissue >5 cm from the tumor margin. We compared the obtained data on the miRNA expression in tumors with data from The Cancer Genome Atlas (TCGA). We found that in 76.7% of non-smoking LAC patients, CYP1A1 mRNA was not detected in tumor and normal lung tissues, while in smoking patients, CYP1A1 expression was detected in tumors in almost half of the cases (47.5% for SCC and 42.5% for LAC). The expression profile of AhR-regulated miRNAs differed between LAC and SCC and depended on the smoking status. In LAC patients, the expression of oncogenic miRNA-21 and miRNA-93 in tumors was higher than in normal lung tissue from the same patients. However, in SCC patients from our sample, the levels of these miRNAs in tumor and non-transformed lung tissue did not differ significantly. The results of our studies and TCGA data indicate that the expression levels of miRNA-181a and miRNA-146a in LAC are associated with smoking: expression of these miRNAs was significantly lower in tumors of smokers. It is possible that their expression is regulated by AhR and AhRR (AhR repressor), and inhibition of AhR by AhRR leads to a decrease in miRNA expression in tumors of smoking patients. Overall, these results confirm that smoking has an effect on the miRNA expression profile. This should be taken into account when searching for new diagnostic and therapeutic targets for NSCLC.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 1","pages":"52-60"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048671","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}
T S Shkrigunov, N E Vavilov, N F Samenkova, Yu S Kisrieva, A L Rusanov, D D Romashin, I I Karuzina, A V Lisitsa, N A Petushkova
{"title":"Identification of protein components of the transformation system in the cell line of immortalized human keratinocytes HaCaT exposed to surfactants.","authors":"T S Shkrigunov, N E Vavilov, N F Samenkova, Yu S Kisrieva, A L Rusanov, D D Romashin, I I Karuzina, A V Lisitsa, N A Petushkova","doi":"10.18097/PBMC20247001061","DOIUrl":"10.18097/PBMC20247001061","url":null,"abstract":"<p><p>Using the method of shotgun mass spectrometry, we have evaluated changes in the proteomic profile of HaCat cells in response to the treatment with sodium dodecyl sulfate (anionic surfactant) and Triton-X100 (non-ionic surfactant) in two concentrations (12.5 µg/ml and 25.0 µg/ml). The study revealed induction of orphan CYP2S1 (biotransformation phase I) in response to Triton-X100. We have identified proteins of II (glutathione-S-transferases, GSTs) and III (solute carrier proteins, SLCs) biotransformation phases, as well as antioxidant proteins (peroxiredoxins, PRDXs; catalase, CAT; thioredoxin, TXN). Thus, proteins of all three xenobiotic detoxification phases were detected. The presented results suggest a new prospect of using HaCaT keratinocytes as a model of human epidermis for studying the metabolism of drugs/toxicants in human skin in vitro.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 1","pages":"61-68"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048673","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 cytotoxic and antiproliferative properties of ruthenium nitrosyl complexes and their modulation effect on cytochrome P450 in the HepG2 cell line.","authors":"L S Klyushova, V A Vavilin, A Yu Grishanova","doi":"10.18097/PBMC20247001033","DOIUrl":"10.18097/PBMC20247001033","url":null,"abstract":"<p><p>Ruthenium nitrosyl complexes are actively investigated as antitumor agents. Evaluation of potential interactions between cytochromes P450 (CYPs) with new compounds is carried out regularly during early drug development. In this study we have investigated the cytotoxic and antiproliferative activities of ruthenium nitrosyl complexes with methyl/ethyl esters of nicotinic and isonicotinic acids and γ-picoline against 2D and 3D cultures of human hepatocellular carcinoma HepG2 and non-cancer human lung fibroblasts MRC-5, assessed their photoinduced activity at λrad = 445 nm, and also evaluated their modulating effect on CYP3A4, CYP2C9, and CYP2C19. The study of cytotoxic and antiproliferative activities against 2D and 3D cell models was performed using phenotypic-based high content screening (HCS). The expression of CYP3A4, CYP2C9, and CYP2C19 mRNAs and CYP3A4 protein was examined using target-based HCS. The results of CYP3A4 mRNA expression were confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). The ruthenium nitrosyl complexes exhibited a dose-dependent cytotoxic effect against HepG2 and MRC-5 cells. The cytotoxic activity of complexes with ethyl isonicotinate (1) and nicotinate (3, 4) was significantly lower for MRC-5 than for HepG2, for a complex with methyl isonicotinate (2) it was higher for MRC-5 than for HepG2, for a complex with γ-picoline (5) it was comparable for both lines. The antiproliferative effect of complexes 2 and 5 was one order of magnitude higher for MRC-5; for complexes 1, 3, and 4 it was comparable for both lines. The cytotoxic activity of all compounds for 3D HepG2 was lower than for 2D HepG2, with the exception of 4. Photoactivation affected the activity of complex 1 only. Its cytotoxic activity decreased, while the antiproliferative activity increased. The ruthenium nitrosyl complexes 1-4 acted as inducers of CYP3A4 and CYP2C19, while the complex with γ-picoline (5) induced of CYP3A4. Among the studied ruthenium nitrosyl complexes, the most promising potential antitumor compound is the ruthenium compound with methyl nicotinate (4).</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 1","pages":"33-40"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048674","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, I G Kapitsa, L Sh Kazieva, N E Vavilov, V G Zgoda, A E Medvedev
{"title":"The delayed effect of rotenone on the relative content of brain isatin-binding proteins of rats with experimental parkinsonism.","authors":"O A Buneeva, I G Kapitsa, L Sh Kazieva, N E Vavilov, V G Zgoda, A E Medvedev","doi":"10.18097/PBMC20247001025","DOIUrl":"10.18097/PBMC20247001025","url":null,"abstract":"<p><p>Isatin (indoldione-2,3) is an endogenous biological regulator found in the brain, peripheral tissues, and biological fluids of humans and animals. Its biological activity is realized via isatin-binding proteins, many of which were identified during proteomic profiling of the brain of mice and rats. A number of these proteins are related to the development of neurodegenerative diseases. Previously, using a model of experimental Parkinsonism induced by a seven-day course of rotenone injections, we have observed behavioral disturbances, as well as changes in the profile and relative content of brain isatin-binding proteins. In this study, we have investigated behavioral responses and the relative content of brain isatin-binding proteins in rats with rotenone-induced Parkinsonism 5 days after the last administration of this neurotoxin. Despite the elimination of rotenone, animals exhibited motor and coordination impairments. Proteomic profiling of isatin-binding proteins revealed changes in the relative content of 120 proteins (the relative content of 83 proteins increased and that of 37 proteins decreased). Comparison of isatin-binding proteins characterized by the changes in the relative content observed in the brain right after the last injection of rotenone (n=16) and 5 days later (n=11) revealed only two common proteins (glyceraldehyde-3-phosphate dehydrogenase and subunit B of V-type proton ATPase). However, most of these proteins are associated with neurodegeneration, including Parkinson's and Alzheimer's diseases.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 1","pages":"25-32"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048675","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}
N Yu Rusetskaya, N Yu Loginova, E P Pokrovskaya, Yu S Chesovskikh, L E Titova
{"title":"Redox regulation of the NLRP3-mediated inflammation and pyroptosis.","authors":"N Yu Rusetskaya, N Yu Loginova, E P Pokrovskaya, Yu S Chesovskikh, L E Titova","doi":"10.18097/PBMC20236906333","DOIUrl":"10.18097/PBMC20236906333","url":null,"abstract":"<p><p>The review considers modern data on the mechanisms of activation and redox regulation of the NLRP3 inflammasome and gasdermins, as well as the role of selenium in these processes. Activation of the inflammasome and pyroptosis represent an evolutionarily conserved mechanism of the defense against pathogens, described for various types of cells and tissues (macrophages and monocytes, microglial cells and astrocytes, podocytes and parenchymal cells of the kidneys, periodontal tissues, osteoclasts and osteoblasts, as well as cells of the digestive and urogenital systems, etc.). Depending on the characteristics of redox regulation, the participants of NLRP3 inflammation and pyroptosis can be subdivided into 2 groups. Members of the first group block the mitochondrial electron transport chain, promote the formation of reactive oxygen species and the development of oxidative stress. This group includes granzymes, the mitochondrial antiviral signaling protein MAVS, and others. The second group includes thioredoxin interacting protein (TXNIP), erythroid-derived nuclear factor-2 (NRF2), Kelch-like ECH-associated protein 1 (Keap1), ninjurin (Ninj1), scramblase (TMEM16), inflammasome regulatory protein kinase NLRP3 (NEK7), caspase-1, gasdermins GSDM B, D and others. They have redox-sensitive domains and/or cysteine residues subjected to redox regulation, glutathionylation/deglutathionylation or other types of regulation. Suppression of oxidative stress and redox regulation of participants in NLRP3 inflammation and pyroptosis depends on the activity of the antioxidant enzymes glutathione peroxidase (GPX) and thioredoxin reductase (TRXR), containing a selenocysteine residue Sec in the active site. The expression of GPX and TRXR is regulated by NRF2 and depends on the concentration of selenium in the blood. Selenium deficiency causes ineffective translation of the Sec UGA codon, translation termination, and, consequently, synthesis of inactive selenoproteins, which can cause various types of programmed cell death: apoptosis of nerve cells and sperm, necroptosis of erythrocyte precursors, pyroptosis of infected myeloid cells, ferroptosis of T- and B-lymphocytes, kidney and pancreatic cells. In addition, suboptimal selenium concentrations in the blood (0.86 μM or 68 μg/l or less) have a significant impact on expression of more than two hundred and fifty genes as compared to the optimal selenium concentration (1.43 μM or 113 μg/l). Based on the above, we propose to consider blood selenium concentrations as an important parameter of redox homeostasis in the cell. Suboptimal blood selenium concentrations (or selenium deficiency states) should be used for assessment of the risk of developing inflammatory processes.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"69 6","pages":"333-352"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048297","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}
V I Fedchenko, A V Veselovsky, A T Kopylov, A E Medvedev
{"title":"The search for potential hypotensive peptides in the amino acid sequence of human renalase and their identification in proteolytic fragments of this protein.","authors":"V I Fedchenko, A V Veselovsky, A T Kopylov, A E Medvedev","doi":"10.18097/PBMC20236906403","DOIUrl":"10.18097/PBMC20236906403","url":null,"abstract":"<p><p>Renalase (RNLS) is a secretory protein discovered in 2005. It plays an important role in the regulation of blood pressure. Studies by two independent laboratories have shown that administration of purified recombinant RNLS reduced blood pressure in experimental animals. However, the mechanisms of the antihypertensive effect of RNLS still remain unclear, especially in the context of the shift in the catalytic paradigm of this protein. In addition, there is growing evidence that endogenous plasma/serum RNLS, detected by enzyme immunoassay, is not an intact protein secreted into the extracellular space, and exogenous recombinant RNLS is effectively cleaved during short-term incubation with human plasma samples. This suggests that the antihypertensive effect of RNLS may be due to peptides formed during proteolytic processing. Based on the results of a bioinformatics analysis of potential RNLS cleavage sites (Fedchenko et al., Medical Hypotheses, 2022; DOI: 10.1016/j.mehy.2022.110895), a number of short peptides have been identified in the RNLS sequence that show similarity to fragments of known peptide inhibitors of angiotensin-converting enzyme. Some of them were found as a part of larger RNLS peptides, formed during RNLS cleavage by chymotrypsin and, and to a lesser extent, by trypsin.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"69 6","pages":"403-408"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048301","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}
S E Novikova, T V Tolstova, N A Soloveva, T E Farafonova, O V Tikhonova, L K Kurbatov, A L Rusanov, V G Zgoda
{"title":"System analysis of surface CD markers during the process of granulocytic differentiation.","authors":"S E Novikova, T V Tolstova, N A Soloveva, T E Farafonova, O V Tikhonova, L K Kurbatov, A L Rusanov, V G Zgoda","doi":"10.18097/PBMC20236906383","DOIUrl":"10.18097/PBMC20236906383","url":null,"abstract":"<p><p>Plasma membrane proteins with extracellular-exposed domains are responsible for transduction of extracellular signals into intracellular responses, and their accessibility to therapeutic molecules makes them attractive targets for drug development. In this work, using omics technologies and immunochemical methods, we have studied changes in the content of markers of clusters of differentiation (CD markers) of neutrophils (CD33, CD97, CD54, CD38, CD18, CD11b, CD44, and CD71) at the level of transcripts and proteins in NB4, HL-60 and K562 cell lines, induced by the treatment with all-trans-retinoic acid (ATRA). Transcriptomic analysis revealed the induction of CD38, CD54, CD11b, and CD18 markers as early as 3 h after the addition of the inducer in the ATRA-responsive cell lines HL-60 and NB4. After 24 h, a line-specific expression pattern of CD markers could be observed in all cell lines. Studies of changes in the content of CD antigens by means of flow cytometry and targeted mass spectrometry (MS) gave similar results. The proteomic profile of the surface markers (CD38, CD54, CD11b, and CD18), characteristic of the NB4 and HL-60 lines, reflects different molecular pathways for the implementation of ATRA-induced differentiation of leukemic cells into mature neutrophils.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"69 6","pages":"383-393"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048299","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}