Acta NaturaePub Date : 2024-01-01DOI: 10.32607/actanaturae.27327
O Y Susova, S S Karshieva, A A Kostyukov, N I Moiseeva, E A Zaytseva, K V Kalabina, E Zusinaite, K Gildemann, N M Smirnov, A F Arutyunyan, A L Zhuze
{"title":"Dimeric Bis-Benzimidazole-Pyrroles DB2Py(n) - AT-Site-Specific Ligands: Synthesis, Physicochemical Analysis, and Biological Activity.","authors":"O Y Susova, S S Karshieva, A A Kostyukov, N I Moiseeva, E A Zaytseva, K V Kalabina, E Zusinaite, K Gildemann, N M Smirnov, A F Arutyunyan, A L Zhuze","doi":"10.32607/actanaturae.27327","DOIUrl":"10.32607/actanaturae.27327","url":null,"abstract":"<p><p>Its broad spectrum of biological activity makes benzimidazole a fundamental pharmacophore in pharmaceutics. The paper describes newly synthesized AT-specific fluorescent bis-benzimidazole molecules DB2Py(n) that contain a pyrrolcarboxamide fragment of the antibiotic drug netropsin. Physico-chemical methods using absorption, fluorescence, and circular dichroism spectra have shown the ability of bis-benzimidazole- pyrroles to form complexes with DNA. The new DB2Py(n) series have turned out to be more toxic to human tumor lines and less vulnerable to non-tumor cell lines. Bis-benzimidazole-pyrroles penetrated the cell nucleus, affected the cell-cycle synthesis (S) phase, and inhibited eukaryotic topoisomerase I in a cellfree model at low concentrations. A real-time tumor cell proliferation test confirmed the molecule's enhanced toxic properties upon dimerization. Preliminary cytotoxicity data for the bis-benzimidazole-pyrroles tested in a cell model with a MDR phenotype showed that monomeric compounds can overcome MDR, while dimerization weakens this ability to its intermediate values as compared to doxorubicin. In this respect, the newly synthesized cytotoxic structures seem promising for further, in-depth study of their properties and action mechanism in relation to human tumor cells, as well as for designing new AT-specific ligands.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"86-100"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta NaturaePub Date : 2024-01-01DOI: 10.32607/actanaturae.27374
D V Shcheblyakov, D V Voronina, I A Favorskaya, I B Esmagambetov, I A Alekseeva, A I Korobkova, E I Ryabova, A A Derkaev, V Yu Kan, A Sh Dzharullaeva, A I Tukhvatulin, A S Bandelyuk, M M Shmarov, D Yu Logunov, A L Gintsburg
{"title":"Broadly Reactive Nanobody Targeting the H3 Hemagglutinin of the Influenza A Virus.","authors":"D V Shcheblyakov, D V Voronina, I A Favorskaya, I B Esmagambetov, I A Alekseeva, A I Korobkova, E I Ryabova, A A Derkaev, V Yu Kan, A Sh Dzharullaeva, A I Tukhvatulin, A S Bandelyuk, M M Shmarov, D Yu Logunov, A L Gintsburg","doi":"10.32607/actanaturae.27374","DOIUrl":"10.32607/actanaturae.27374","url":null,"abstract":"<p><p>Monoclonal antibodies and recombinant antibody fragments are a very promising therapeutic tool to combat infectious diseases. Due to their unique paratope structure, nanobodies (VHHs) hold several advantages over conventional monoclonal antibodies, especially in relation to viral infections. Influenza A viruses (IAVs) remain a major threat to public health. The hemagglutinin (HA) protein is the main protective and immunodominant antigen of IAVs. In this study, three broadly reactive nanobodies (D9.2, E12.2, and D4.2) to H3N2 influenza strains were isolated and Fc-fusion proteins (VHH-Fcs) were obtained and characterized <i>in vitro</i>. This modification improved the nanobodies' binding activity and allowed for their interaction with a wider range of strains. The D9.2-Fc antibody showed a 100% protection rate against mortality <i>in vivo</i> in a mouse lethal model. Furthermore, we demonstrated that the observed protection has to do with Fc-FcγR interactions. These results indicate that D9.2-Fc can serve as an effective antiviral agent against the H3N2 influenza infection.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"16 1","pages":"101-110"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta NaturaePub Date : 2023-10-11DOI: 10.5852/naturae2023a7
Iris LANG, Camille GILLIOT, Olivier SCHER, Laurent PONTCHARRAUD, Daniel MARC
{"title":"Création d’une liste régionale catégorisée d’espèces exotiques envahissantes et pistes d’utilisation pour les gestionnaires d’espaces naturels","authors":"Iris LANG, Camille GILLIOT, Olivier SCHER, Laurent PONTCHARRAUD, Daniel MARC","doi":"10.5852/naturae2023a7","DOIUrl":"https://doi.org/10.5852/naturae2023a7","url":null,"abstract":"Les espèces exotiques envahissantes (EEE) constituent une des cinq causes majeures d’érosion de la biodiversité à l’échelle mondiale. Devant leur diversité et leur abondance, il est impossible d’agir sur toutes les EEE. Le règlement UE 1143/2014 et la stratégie nationale relative aux EEE de 2017 offrent un cadre pour la prévention de l’introduction et de la propagation des EEE et leur gestion. Le Conservatoire d’Espaces naturels d’Occitanie a élaboré et anime actuellement la stratégie régionale relative aux EEE Faune d’Occitanie, dont l’objectif est d’orienter et de coordonner les actions menées vis-à-vis de ces espèces. Un état des lieux des connaissances des EEE Faune présentes ou susceptibles d’être introduites en Occitanie a d’abord été réalisé. Il n’existe pas, à l’heure actuelle, de méthode standardisée partagée par tous les acteur·rice·s pour classer ces espèces selon la menace qu’elles représentent. Une méthode intégrative a donc été développée à partir de quatre méthodes standardisées internationales et régionales (EICAT, SEICAT, ISEIA, ISSIA) afin de catégoriser les espèces exotiques en Occitanie selon leur potentiel d’invasion et leurs impacts écologiques, socio-économiques et sanitaires. L’objectif de cet article est de partager notre retour d’expérience sur le développement de la méthode pour l’élaboration de la liste catégorisée, et sur les utilisations possibles de cette dernière. Nous montrons notamment comment les acteur·rice·s régionaux, peuvent s’approprier la liste catégorisée, qui constitue le premier outil de connaissance sur les EEE Faune en Occitanie. Les catégories ainsi définies, associées au regard de l’expert·e selon le contexte, permettent d’identifier les grands types d’actions à mener sur ces espèces (prévention, gestion, amélioration des connaissances, communication). Ce travail, qui peut servir aux autres régions déclinant la stratégie nationale, offre un cadre pour l’articulation des stratégies régionales et l’amélioration des modes d’organisation au niveau national.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136210398","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}
Acta NaturaePub Date : 2023-10-01DOI: 10.32607/actanaturae.26551
S A Golyshev, E P Kazakov, I I Kireev, D G Reunov, I V Malyshev
{"title":"Soft X-ray Microscopy in Cell Biology: Current Status, Contributions and Prospects.","authors":"S A Golyshev, E P Kazakov, I I Kireev, D G Reunov, I V Malyshev","doi":"10.32607/actanaturae.26551","DOIUrl":"10.32607/actanaturae.26551","url":null,"abstract":"<p><p>The recent advances achieved in microscopy technology have led to a significant breakthrough in biological research. Super-resolution fluorescent microscopy now allows us to visualize subcellular structures down to the pin-pointing of the single molecules in them, while modern electron microscopy has opened new possibilities in the study of protein complexes in their native, intracellular environment at near-atomic resolution. Nonetheless, both fluorescent and electron microscopy have remained beset by their principal shortcomings: the reliance on labeling procedures and severe sample volume limitations, respectively. Soft X-ray microscopy is a candidate method that can compensate for the shortcomings of both technologies by making possible observation of the entirety of the cellular interior without chemical fixation and labeling with an isotropic resolution of 40-70 nm. This will thus bridge the resolution gap between light and electron microscopy (although this gap is being narrowed, it still exists) and resolve the issue of compatibility with the former, and possibly in the near future, the latter methods. This review aims to assess the current state of soft X-ray microscopy and its impact on our understanding of the subcellular organization. It also attempts to look into the future of X-ray microscopy, particularly as relates to its seamless integration into the cell biology toolkit.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 4","pages":"32-43"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta NaturaePub Date : 2023-10-01DOI: 10.32607/actanaturae.27331
E I Shramova, A Yu Frolova, V P Filimonova, S M Deyev, G M Proshkina
{"title":"System for Self-excited Targeted Photodynamic Therapy Based on the Multimodal Protein DARP-NanoLuc-SOPP3.","authors":"E I Shramova, A Yu Frolova, V P Filimonova, S M Deyev, G M Proshkina","doi":"10.32607/actanaturae.27331","DOIUrl":"10.32607/actanaturae.27331","url":null,"abstract":"<p><p>Despite the significant potential of photodynamic therapy (PDT) as a minimally invasive treatment modality, the use of this method in oncology has remained limited due to two serious problems: 1) limited penetration of the excitation light in tissues, which makes it impossible to affect deep-seated tumors and 2) use of chemical photosensitizers that slowly degrade in the body and cause photodermatoses and hyperthermia in patients. To solve these problems, we propose a fully biocompatible targeted system for PDT that does not require an external light source. The proposed system is based on bioluminescent resonance energy transfer (BRET) from the oxidized form of the luciferase substrate to the photosensitizing protein SOPP3. The BRET-activated system is composed of the multimodal protein DARP-NanoLuc-SOPP3, which contains a BRET pair NanoLuc-SOPP3 and a targeting module DARPin. The latter provides the interaction of the multimodal protein with tumors overexpressing tumor-associated antigen HER2 (human epidermal growth factor receptor type II). <i>In vitro</i> experiments in a 2D monolayer cell culture and a 3D spheroid model have confirmed HER2-specific photo-induced cytotoxicity of the system without the use of an external light source; in addition, experiments in animals with subcutaneous HER2-positive tumors have shown selective accumulation of DARP-NanoLuc-SOPP3 on the tumor site. The fully biocompatible system for targeted BRET-induced therapy proposed in this work makes it possible to overcome the following limitations: 1) the need to use an external light source and 2) the side phototoxic effect from aberrant accumulation of chemical photosensitizers. The obtained results demonstrate that the fully protein-based self-excited BRET system has a high potential for targeted PDT.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 4","pages":"100-110"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta NaturaePub Date : 2023-10-01DOI: 10.32607/actanaturae.25442
O A Averina, S A Kuznetsova, O A Permyakov, P V Sergiev
{"title":"Animal Models of Mitochondrial Diseases Associated with Nuclear Gene Mutations.","authors":"O A Averina, S A Kuznetsova, O A Permyakov, P V Sergiev","doi":"10.32607/actanaturae.25442","DOIUrl":"10.32607/actanaturae.25442","url":null,"abstract":"<p><p>Mitochondrial diseases (MDs) associated with nuclear gene mutations are part of a large group of inherited diseases caused by the suppression of energy metabolism. These diseases are of particular interest, because nuclear genes encode not only most of the structural proteins of the oxidative phosphorylation system (OXPHOS), but also all the proteins involved in the OXPHOS protein import from the cytoplasm and their assembly in mitochondria. Defects in any of these proteins can lead to functional impairment of the respiratory chain, including dysfunction of complex I that plays a central role in cellular respiration and oxidative phosphorylation, which is the most common cause of mitopathologies. Mitochondrial diseases are characterized by an early age of onset and a progressive course and affect primarily energy-consuming tissues and organs. The treatment of MDs should be initiated as soon as possible, but the diagnosis of mitopathologies is extremely difficult because of their heterogeneity and overlapping clinical features. The molecular pathogenesis of mitochondrial diseases is investigated using animal models: i.e. animals carrying mutations causing MD symptoms in humans. The use of mutant animal models opens new opportunities in the study of genes encoding mitochondrial proteins, as well as the molecular mechanisms of mitopathology development, which is necessary for improving diagnosis and developing approaches to drug therapy. In this review, we present the most recent information on mitochondrial diseases associated with nuclear gene mutations and animal models developed to investigate them.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 4","pages":"4-22"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta NaturaePub Date : 2023-10-01DOI: 10.32607/actanaturae.26879
A Yu Frolova, S V Kutyakov, V I Martynov, S M Deyev, A A Pakhomov
{"title":"BODIPY Dye Derivative for Irreversible Fluorescent Labeling of Eukaryotic Cells and Their Simultaneous Cytometric Analysis.","authors":"A Yu Frolova, S V Kutyakov, V I Martynov, S M Deyev, A A Pakhomov","doi":"10.32607/actanaturae.26879","DOIUrl":"10.32607/actanaturae.26879","url":null,"abstract":"<p><p>In this work, we synthesized a green fluorescent dye derivative, 1,3,5,7-tetramethyl-BODIPY, with a heptyl substituent at the 8-position. The obtained highly hydrophobic compound was able to rapidly and irreversibly bind to eukaryotic cells. Incubation of cells with the dye over different periods of time or at different concentrations allowed us to control the degree of cell labeling and the level of fluorescence. This made it possible to modulate the fluorescence level of different eukaryotic cell cultures and then distinguish them by their level of fluorescence signal in the green channel in cytometric experiments. The labeled cells can be combined and further analyzed in the same test tube under identical conditions using the channels in which the dye does not fluoresce. This approach has been tested on a number of tumor cell cultures containing the HER2 receptor on their surface. The representation of the receptor in these cells was analyzed in one test tube in one run using a HER2-specific ligand based on the hybrid protein DARPin9_29-mCherry, which fluoresces in the red region of the spectrum.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 4","pages":"92-99"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta NaturaePub Date : 2023-10-01DOI: 10.32607/actanaturae.26623
A N Narovlyansky, M V Filimonova, N G Tsyshkova, A V Pronin, T V Grebennikova, E V Karamov, V F Larichev, G V Kornilayeva, I T Fedyakina, I V Dolzhikova, M V Mezentseva, E I Isaeva, V V Poloskov, L S Koval, V P Marinchenko, V I Surinova, A S Filimonov, A A Shitova, O V Soldatova, A V Sanin, I K Zubashev, A V Ponomarev, V V Veselovsky, V V Kozlov, A V Stepanov, A V Khomich, V S Kozlov, S A Ivanov, P V Shegai, A D Kaprin, F I Ershov, A L Gintsburg
{"title":"In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2.","authors":"A N Narovlyansky, M V Filimonova, N G Tsyshkova, A V Pronin, T V Grebennikova, E V Karamov, V F Larichev, G V Kornilayeva, I T Fedyakina, I V Dolzhikova, M V Mezentseva, E I Isaeva, V V Poloskov, L S Koval, V P Marinchenko, V I Surinova, A S Filimonov, A A Shitova, O V Soldatova, A V Sanin, I K Zubashev, A V Ponomarev, V V Veselovsky, V V Kozlov, A V Stepanov, A V Khomich, V S Kozlov, S A Ivanov, P V Shegai, A D Kaprin, F I Ershov, A L Gintsburg","doi":"10.32607/actanaturae.26623","DOIUrl":"10.32607/actanaturae.26623","url":null,"abstract":"<p><p>The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012-2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy) carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 <i>in vitro</i>. At a concentration of 52.0 μM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility - high activity (IC<sub>50</sub> = 1.06 μg/mL) and high selectivity index (SI = 78.6) - this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 4","pages":"83-91"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta NaturaePub Date : 2023-10-01DOI: 10.32607/actanaturae.25441
A V Mashkovskaia, S S Mariasina, M V Serebryakova, M P Rubtsova, O A Dontsova, P V Sergiev
{"title":"Testing a Hypothesis of 12S rRNA Methylation by Putative METTL17 Methyltransferase.","authors":"A V Mashkovskaia, S S Mariasina, M V Serebryakova, M P Rubtsova, O A Dontsova, P V Sergiev","doi":"10.32607/actanaturae.25441","DOIUrl":"10.32607/actanaturae.25441","url":null,"abstract":"<p><p>Mitochondrial ribosome assembly is a complex multi-step process involving many additional factors. Ribosome formation differs in various groups of organisms. However, there are universal steps of assembly and conservative factors that have been retained in evolutionarily distant taxa. METTL17, the object of the current study, is one of these conservative factors involved in mitochondrial ribosome assembly. It is present in both bacteria and the mitochondria of eukaryotes, in particular mice and humans. In this study, we tested a hypothesis of putative METTL17 methyltransferase activity. MALDI-TOF mass spectrometry was used to evaluate the methylation of a putative METTL17 target - a 12S rRNA region interacting with METTL17 during mitochondrial ribosome assembly. The investigation of METTL17 and other mitochondrial ribosome assembly factors is of both fundamental and practical significance, because defects in mitochondrial ribosome assembly are often associated with human mitochondrial diseases.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 4","pages":"75-82"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta NaturaePub Date : 2023-10-01DOI: 10.32607/actanaturae.19426
O K Gasymov, M J Bakhishova, R B Aslanov, L A Melikova, J A Aliyev
{"title":"Membrane Partitioning of TEMPO Discriminates Human Lung Cancer from Neighboring Normal Cells.","authors":"O K Gasymov, M J Bakhishova, R B Aslanov, L A Melikova, J A Aliyev","doi":"10.32607/actanaturae.19426","DOIUrl":"10.32607/actanaturae.19426","url":null,"abstract":"<p><p>The plasma membranes of normal and cancer cells of the lung, breast, and colon tissues show considerably different lipid compositions that greatly influence their physicochemical properties. Partitioning of the spin probe 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) into the membranes of human lung normal and carcinoma cells was assessed by EPR spectroscopy to estimate the impact of the lipid compositions. The goal was to reveal potential strategies for cancer therapy attributable to the membrane properties. The study was conducted at pH values of 7.3 and 6.2, relevant to the microenvironments of normal and cancer cells, respectively. The TEMPO partitioning was examined in the temperature interval of 283-317K to reveal the efficacy of local hyperthermia used in chemotherapy. Results indicate that the TEMPO partitioning coefficient for the membranes of human lung carcinoma cells is significantly higher compared with that of neighboring normal cells. Increased partition coefficients were observed at relatively higher temperatures in both normal and cancer cells. However, compared to the normal cells, the cancer cells demonstrated higher partition coefficients in the studied temperature range. The data obtained with C12SL (spin-labeled analog of lauric acid) indicate that increased membrane dynamics of the cancer cells is a possible mechanism for enhanced partitioning of TEMPO. Free energy values for partitioning estimated for pH values of 6.2 and 7.3 show that TEMPO partitioning requires 30% less energy in the cancer cells at pH 7.3. TEMPO and its derivatives have previously been considered as theranostic agents in cancer research. Data suggest that TEMPO derivatives could be used to test if complementary alkalization therapy is effective for cancer patients receiving standard chemotherapy with local hyperthermia.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"15 4","pages":"111-120"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}