Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry最新文献

{"title":"Possibilities of in Silico Estimations for the Development of the Pharmaceutical Composition Phytoladaptogene Cytotoxic for Bladder Cancer Cells","authors":"N. S. Ionov,&nbsp;M. A. Baryshnikova,&nbsp;E. V. Bocharov,&nbsp;P. V. Pogodin,&nbsp;A. A. Lagunin,&nbsp;D. A. Filimonov,&nbsp;R. V. Karpova,&nbsp;V. S. Kosorukov,&nbsp;I. S. Stilidi,&nbsp;V. B. Matveev,&nbsp;O. A. Bocharova,&nbsp;V. V. Poroikov","doi":"10.1134/S1990750821040041","DOIUrl":"10.1134/S1990750821040041","url":null,"abstract":"<p>The priority direction of the pharmaceutical composition Phytoladaptogene (PLA) development based on the prediction of biological activity spectra for several secondary metabolites of medicinal plants using the PASS computer program and validation in vitro of the prediction result was determined. PLA is a complex of structurally diverse small organic compounds including biologically active substances of phytoadaptogenes (ginsenosides from <i>Panax ginseng</i>, rhodionin from <i>Rhodiola rosea</i> and others) compiled considering previously developed pharmaceutical compositions. Two variants of the pharmaceutical composition were studied—major (22 compounds) and minor (13 compounds) ones. The probability of activity exceeds the probability of inactivity for 1400 out of 1945 pharmacological effects and mechanisms predicted by PASS for the major version of PLA. The wide range of predicted activities is mainly due to the compounds' low structural similarity to each other. An in silico prediction indicates the possibilities of antitumor properties against bladder, stomach, colon, ovarian and cervical cancers both for minor and major PLA compositions. It was found that the highest probability values of activity are predicted for three mechanisms: Apoptosis agonist, Caspase 3 stimulant, and Transcription factor NF kappa B inhibitor. According to the PharmaExpert program, they are associated with the antitumor effect against bladder cancer. Experimental validation was performed in vitro on the human bladder cancer cell line RT-112. As a result of the MTT test the cytotoxicity of the PLA major variant was found to be higher than that of the minor one. In the in vitro experiments using two methods—double staining with annexin V and propidium iodide as well as detection of active caspase 3 in cells—the death of bladder cancer cells by the apoptosis mechanism was also confirmed. The data obtained correspond to the results of the prediction and indicate the major PLA composition advantages. Phytoladaptogene can become the basis for the development of a drug with antitumor activity against bladder cancer. Antitumor activity predicted by PASS for other cancers may be the subject of further studies.</p>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"15 4","pages":"290 - 300"},"PeriodicalIF":0.6,"publicationDate":"2021-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4100579","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 Consensus Ensemble Neural Network Multitarget Model of the RAGE Inhibitory Activity of Chemical Compounds","authors":"P. M. Vassiliev,&nbsp;A. A. Spasov,&nbsp;A. N. Kochetkov,&nbsp;M. A. Perfilev,&nbsp;A. R. Koroleva","doi":"10.1134/S1990750821040107","DOIUrl":"10.1134/S1990750821040107","url":null,"abstract":"<p>RAGE signal transduction via the RAGE-NF-κB signaling pathway is one of the mechanisms of inflammatory reactions that cause severe diabetic complications. RAGE inhibitors are promising pharmacological compounds; their development requires creation of new predictive models. Based on the methodology of artificial neural networks, a consensus ensemble neural network multitarget model has been constructed. This model describes the dependence of the RAGE inhibitory activity on the affinity of compounds for 34 target proteins of the RAGE-NF-κB signal pathway. For this purpose an expanded database of valid three-dimensional models of target proteins of the RAGE-NF-κB signal chain has been created using the database of three-dimensional models of relevant biotargets. Ensemble molecular docking of known RAGE inhibitors from the verified database into the sites of added models of target proteins was performed, and the minimum docking energies for each compound in relation to each target were determined. An extended training set for neural network modeling was formed. Using seven variants of learning by the method of artificial multilayer perceptron neural networks, three ensembles of classification decision rules were constructed to predict three level of the RAGE-inhibitory activity based on the calculated affinity of compounds for significant target proteins of the RAGE-NF-κB signaling pathway. Using a simple consensus of the second level, the predictive ability of the created model was assessed and its high accuracy and statistical significance were demonstrated. The resultant consensus ensemble neural network multitarget model has been used for virtual screening of new derivatives of different chemical classes. The most promising substances have been synthesized and sent for experimental studies.</p>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"15 4","pages":"281 - 289"},"PeriodicalIF":0.6,"publicationDate":"2021-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4100765","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 Effect of Glucocorticoids in Combination with Azithromycin or Theophylline on Cytokine Production by NK and NKT-Like Blood Cells of Patients with Chronic Obstructive Pulmonary Disease","authors":"A. G. Kadushkin,&nbsp;A. D. Tahanovich,&nbsp;L. V. Movchan,&nbsp;T. S. Kolesnikova,&nbsp;E. V. Khadasouskaya,&nbsp;T. V. Shman","doi":"10.1134/S1990750821040053","DOIUrl":"10.1134/S1990750821040053","url":null,"abstract":"<p>Chronic obstructive pulmonary disease (COPD) is characterized by reduced sensitivity of cells to the anti-inflammatory effects of glucocorticoids (GCs). Azithromycin and a low dose theophylline have a significant impact on molecular mechanisms leading to corticosteroid resistance. The aim of this study was to evaluate the ability of azithromycin and theophylline to enhance the anti-inflammatory effects of GCs on the production of cytokines by NK and NKT-like blood cells of COPD patients. Whole blood cells from COPD patients (<i>n</i> = 21) were incubated in the presence of budesonide (10 nM), azithromycin (10 μg/mL), theophylline (1 μM), or their combinations and stimulated with phorbol myristate acetate (50 ng/mL). Intracellular production of proinflammatory cytokines in NK (CD3-CD56+) and NKT-like (CD3+CD56+) blood cells was analyzed by flow cytometry. Budesonide reduced synthesis of interleukin 4 (IL-4), CXCL8, tumor necrosis factor α (TNFα) by NK and NKT-like cells, as well as production of interferon γ (IFNγ) by NK cells. Azithromycin suppressed production of IL-4 and CXCL8 by NK and NKT-like cells, and theo-phylline inhibited IL-4 synthesis by these lymphocytes. The combination of azithromycin and budesonide had a more pronounced inhibitory effect on the production of IL-4 and CXCL8 by NK and NKT-like cells than the effect of these drugs alone. The combination of theophylline and budesonide suppressed synthesis of IL-4 and CXCL8 by NK and NKT-like cells, as well as the production of TNFα and IFNγ by NK cells stronger than budesonide alone. The obtained results demonstrate the benefits for the combined use of GCs with theophylline at a low dose or azithromycin to suppress the inflammatory process in patients with COPD.</p>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"15 4","pages":"337 - 344"},"PeriodicalIF":0.6,"publicationDate":"2021-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4100129","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":"Prediction of Metabolic Stability of Xenobiotics by the Pass and Gusar Programs","authors":"E. I. Korotkevich,&nbsp;A. V. Rudik,&nbsp;A. V. Dmitriev,&nbsp;A. A. Lagunin,&nbsp;D. A. Filimonov","doi":"10.1134/S1990750821040089","DOIUrl":"10.1134/S1990750821040089","url":null,"abstract":"<p>Metabolic stability determines the susceptibility of compounds to biotransformation on the body. It is characterized by such parameters as half-life (<i>T</i>_1/2) and clearance (CL). In vitro systems based on cells or subcellular fractions (mainly liver microsomal enzymes) are consider as models of processes occurring in a living organism and are used for metabolic stability assessment. The data obtained from the experiments are used to build QSAR models. Based on the freely available database ChEMBL v.27, we collected more than 8000 records containing the structures of compounds and their clearance and/or half-life time values obtained on human liver microsomes. GUSAR (General Unrestricted Structure-Activity Relationships) and PASS (Prediction of Activity Spectra for Substances) software were used to create quantitative and qualitative models based on the collected data. A 5-fold cross-validation procedure was used to the model assessments. Thresholds <i>T</i>_1/2 = 30 min and CL = 20 mL/min/kg were chosen to distinguish between stable and unstable molecules. The accuracy of the models changes from 0.5 (calculated using 5-fold cross-validation on quantitative models for predicting the half-life) to 0.96 (calculated using 5-fold cross-validation on classification models for predicting the clearance).</p>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"15 4","pages":"301 - 305"},"PeriodicalIF":0.6,"publicationDate":"2021-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4100146","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":"Changes in the Mitochondrial Subproteome of Mouse Brain Rpn13-Binding Proteins Induced by the Neurotoxin MPTP and the Neuroprotector Isatin","authors":"O. A. Buneeva,&nbsp;A. T. Kopylov,&nbsp;O. V. Gnedenko,&nbsp;M. V. Medvedeva,&nbsp;I. G. Kapitsa,&nbsp;E. A. Ivanova,&nbsp;A. S. Ivanov,&nbsp;A. E. Medvedev","doi":"10.1134/S1990750821030021","DOIUrl":"10.1134/S1990750821030021","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>Mitochondrial dysfunction and ubiquitin-proteasome system (UPS) failure contribute significantly to the development of Parkinson’s disease (PD). The proteasome subunit Rpn13 located on the regulatory (19S) subparticle plays an important role in the delivery of proteins, subjected to degradation, to the proteolytic (20S) part of proteasome. We have previously found several brain mitochondrial proteins specifically bound to Rpn13 (Buneeva et al., <i>Biochemistry</i> (<i>Moscow</i>), <i>Supplement Series B: Biomedical Chemistry</i>, (2020), vol. 14, pp. 297−305). In this study we have investigated the effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the neuroprotector isatin on the mitochondrial subproteome of Rpn13-binding proteins of the mouse brain. Administration of MPTP (30 mg/kg) to animals caused movement disorders typical of PD, while pretreatment with isatin (100 mg/kg, 30 min before MPTP) reduced their severity. At the same time, the injection of MPTP, isatin, or their combination (isatin + MPTP) had a significant impact on the total number and the composition of Rpn13-binding proteins. The injection of MPTP decreased the total number of Rpn13-binding proteins in comparison with control, and the injection of isatin prior to MPTP or without MPTP caused an essential increase in the number of Rpn13-binding proteins, mainly of the functional group of proteins participating in the protein metabolism regulation, gene expression, and cell division and differentiation. Selected biosensor validation confirmed the interaction of the proteasome Rpn13 subunit with some proteins (glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, histones H2A and H2B) recognized during proteomic profiling. The results obtained suggest that under the conditions of experimental MPTP-induced parkinsonism the neuroprotective effect of isatin may be aimed at the interaction of mitochondria with the components of UPS.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"15 3","pages":"199 - 214"},"PeriodicalIF":0.6,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4640716","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":"Interaction Study of Different Forms of Human Recombinant Anti-Mullerian Hormone with a Chimeric Analogue of the AMH Type II Receptor","authors":"A. Ya. Rak,&nbsp;A. V. Trofimov,&nbsp;A. M. Ischenko,&nbsp;A. V. Sokolov","doi":"10.1134/S1990750821030082","DOIUrl":"10.1134/S1990750821030082","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>Anti-mullerian hormone (AMH), a homodimeric glycoprotein, described over 70 years ago by A. Jost, is the least studied member of the transforming growth factor beta superfamily. Despite the antitumor activity of AMH discovered at the end of the last century, creation of effective AMH-based drugs is hampered primarily by the lack of information on the mechanism of interaction of various AMH forms with a specific type II receptor (MISRII). Previously, we have shown that not only the full-length activated hormone but also its C-terminal fragment (C-rAMH) could bind to MISRII. In this work, using the surface plasmon resonance technique, we have compared the interaction of three forms of recombinant AMH (rAMH) with the MISRII analogue—the chimeric protein MISRII-Fc containing AMH type II receptor and-Fc fragment of the human IgG1 heavy chain. Comparison of the binding of MISRII-Fc, immobilized on a chip with group specificity for human immunoglobulins, to C-rAMH, to intact rAMH (pro-rAMH), and to rAMH containing one uncleaved monomer (hc-rAMH), showed that the <i>K</i>_D of the complexes increased: 1.7 nM, 88 nM and 110 nM, respectively. Thus, we have shown that the C-terminal fragment of AMH exhibits the maximum affinity for the recombinant MISRII analogue, thus indicating the prospects for the development of drugs based on this hormone derivative.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"15 3","pages":"232 - 240"},"PeriodicalIF":0.6,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4638161","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":"Features of the In Vitro Expression Profile of Hippocampal Neurogenic Niche Cells during Optogenetic Stimulation","authors":"E. D. Khilazheva,&nbsp;A. V. Morgun,&nbsp;E. B. Boytsova,&nbsp;A. I. Mosiagina,&nbsp;A. N. Shuvaev,&nbsp;N. A. Malinovskaya,&nbsp;Yu. A. Uspenskaya,&nbsp;E. A. Pozhilenkova,&nbsp;A. B. Salmina","doi":"10.1134/S1990750821030057","DOIUrl":"10.1134/S1990750821030057","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>In the central nervous system of mammals, there are specialized areas, known as neurogenic niches, in which neurogenesis is observed in the postnatal period. It is believed that astrocytes in the composition of neurogenic niches play a significant role in the regulation of neurogenesis, and therefore they are considered as a promising “target” for the possible control of neurogenesis, including the use of optogenetics. In the framework of this study, we have formed an in vitro model of a neurogenic niche, consisting of cerebral endothelial cells, astrocytes, and neurospheres. Astrocytes in the neurogenic niche model expressed channelrhodopsin ChR2 and underwent photoactivation. The effect of photoactivated astrocytes on the expression profile of neurogenic niche cells was evaluated using methods of immunocytochemical analysis. It was found that intact astrocytes in the composition of the neurogenic niche promoted neuronal differentiation of stem cells, as well as the activation of astroglia expressing photosensitive proteins, changed expression of molecules characterized by intercellular interactions of pools of resting and proliferating cells in the composition of the neurogenic niche with the participation of NAD⁺ (Cx43, CD38, CD157), lactate (MCT1). The registered changes reflect: (i) impaired paracrine interactions between two subpopulations of cells, one of which acts as a source of NAD⁺, and another one is a consumer of NAD⁺ required for processes of the intracellular signal transduction; (ii) changes in the mechanisms of lactate transport due to aberrant expression of the lactate transporter MCT1 in cells forming a pool of cells developing along the neuronal path of differentiation (but not neuronal stem cells). In general, during photostimulation of niche astrocytes, the total proliferative activity increases mainly due to neural progenitor cells, but not neural stem cells. Thus, optogenetic activation of astrocytes can become a promising tool for controlling the activity of neurogenesis processes and the formation of a local proneurogenic microenvironment in an in vitro model of the neurogenic niche.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"15 3","pages":"224 - 231"},"PeriodicalIF":0.6,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4636237","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":"Haptoglobin as a Biomarker","authors":"S. N. Naryzny,&nbsp;O. K. Legina","doi":"10.1134/S1990750821030069","DOIUrl":"10.1134/S1990750821030069","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>Haptoglobin (Hp) is a glycoprotein that binds free hemoglobin (Hb) in plasma and plays a critical role in tissue protection and prevention of oxidative damage. Besides, it has some regulatory functions. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein synthesized mainly in the liver and lungs and is the subject of research as a potential biomarker of many diseases, including various forms of malignant neoplasms. Haptoglobin has several unique biophysical characteristics. The human <i>Нр</i> gene is polymorphic, has three structural alleles that control the synthesis of three major phenotypes of haptoglobin: homozygous Нр1-1 and Нр2-2, and heterozygous Нр2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual predisposition of a person to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). These are structural transformations (removal of the signal peptide, cutting off the Pre-Hp precursor molecule into two subunits, α and β, limited proteolysis of α-chains, formation of disulfide bonds, multimerization), as well as chemical modifications of α-chains and glycosylation of the β-chain. Glycosylation of the β-chain of haptoglobin at four Asn sites is the most important variable PTM that regulates the structure and function of the glycoprotein. The study of modified oligosaccharides of the β-chain of Hp has become the main direction in the study of pathological processes, including malignant neoplasms. These characteristics indicate the possibility of the existence of Hp in the form of a multitude of proteoforms, probably performing different functions. This review is devoted to the description of the structural and functional diversity and the potential use of Hp as a biomarker of various pathologies.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"15 3","pages":"184 - 198"},"PeriodicalIF":0.6,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1990750821030069.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4638148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of the Side Population Associated with ATP-Binding Cassette Transporters Activity Using Imaging Flow Cytometry","authors":"A. M. Gisina,&nbsp;Y. S. Kim,&nbsp;K. N. Yarygin,&nbsp;A. Yu. Lupatov","doi":"10.1134/S1990750821030033","DOIUrl":"10.1134/S1990750821030033","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>DyeCycle Violet efflux, caused by ATP-binding cassette transporters activity, was analyzed in human colorectal adenocarcinoma cell lines SW480, HT-29, Caco-2 by means of a FACSAria III flow cytometer and an ImageStreamX Mk II imaging flow cytometer. Besides similarity of cytometry data obtained by two instruments, the use of imaging flow cytometry made it possible to characterize the morphology of side population cells, as well as morphology of other cell populations differing in the degree of dye accumulation. The population of cells, which are smaller than the side population cells and practically do not take the dye, is of the special interest. Probably, this population may contribute to the tumor resistance to chemotherapy.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"15 3","pages":"248 - 254"},"PeriodicalIF":0.6,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4638162","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 Gene Expression Profile in Endothelial Cells Exposed to Mitomycin C","authors":"M. Yu. Sinitsky,&nbsp;A. V. Tsepokina,&nbsp;A. G. Kutikhin,&nbsp;D. K. Shishkova,&nbsp;A. V. Ponasenko","doi":"10.1134/S1990750821030100","DOIUrl":"10.1134/S1990750821030100","url":null,"abstract":"<div><div><h3>\u0000 <b>Abstract</b>—</h3><p>The expression of genes involved in DNA repair (<i>DDB1</i>, <i>ERCC4</i>, <i>ERCC5</i>), leukocyte adhesion (<i>VCAM1</i>, <i>ICAM1</i>, <i>SELE</i>, <i>SELP</i>), endothelial mechanotransduction (<i>KLF4</i>), endothelial differentiation (<i>PECAM1</i>, <i>CDH5</i>, <i>CD34</i>, <i>NOS3</i>), endothelial-to-mesenchymal transition (<i>SNAI1</i>, <i>SNAI2</i>, <i>TWIST1</i>, <i>GATA4</i>, <i>ZEB1</i>, <i>CDH2</i>), and also coding scavenger-receptors (<i>LOX1</i>, <i>SCARF1</i>, <i>CD36</i>, <i>LDLR</i>, <i>VLDR</i>), antioxidant system (<i>PXDN</i>, <i>CAT</i>, <i>SOD1</i>) and transcription factor (<i>HEY2</i>) has been studied using the quantitative PCR in primary human coronary (HCAEC) and internal thoracic (HITAEC) arteries endothelial cells exposed to alkylating mutagen mitomycin C (MMC). The study was carried out two time points after 6 h of incubation with MMC and after 6 h of the genotoxic load followed by 24 h of incubation in pure culture medium. After the exposure to MMC, a decreased expression of almost all studied genes was noted in the exposed HCAEC and HITAEC; the only exception was found in the case of <i>SNAI2</i>, which demonstrated a 4-fold increase in its expression compared to the unexposed control. Elimination of MMC from the both cell cultures was accompanied by increased expression of the <i>VCAM1</i>, <i>ICAM1</i>, <i>SELE</i>, <i>SNAI2</i>, <i>KLF4</i> genes and decreased expression of the <i>PECAM1</i>, <i>CDH5</i>, <i>CD34</i>, <i>ZEB1</i>, <i>CAT</i>, <i>PXDN</i> genes. In addition, HITAEC cells were characterized by decreased expression of the <i>SOD1</i>, <i>SCARF1</i>, <i>CD36</i> genes and an increased expression of the <i>SNAI1</i> and <i>TWIST1</i> genes; in HCAEC, increased expression of the <i>LDLR</i> and <i>VLDLR</i> genes was noted. Thus, the genotoxic stress, induced by the alkylating mutagen MMC, is associated with the endothelial dysfunction, manifested by the altered gene expression profile of the endothelial cell cultivated under conditions of the genotoxic load.</p></div></div>","PeriodicalId":485,"journal":{"name":"Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry","volume":"15 3","pages":"255 - 261"},"PeriodicalIF":0.6,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4638176","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}