44 results on '"Zinovkin, Roman A."'
Search Results
2. A New Mouse Strain with a Mutation in the NFE2L2 (NRF2) Gene
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Egorov, Evgeniy S., Kondratenko, Natalia D., Averina, Olga A., Permyakov, Oleg A., Emelyanova, Maria A., Prikhodko, Anastasia S., Zinovkina, Ludmila A., Sergiev, Petr V., and Zinovkin, Roman A.
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- 2023
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3. Challenges of using microRNAs as potential disease biomarkers. A review
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Zinovkin, Roman A. and Sakharov, Ivan Yu.
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- 2024
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4. Phenoptosis. Preface to the Special Issue
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Zinovkin, Roman A.
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- 2023
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5. Does Nrf2 Play a Role of a Master Regulator of Mammalian Aging?
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Zinovkin, Roman A., Kondratenko, Natalia D., and Zinovkina, Ludmila A.
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- 2022
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6. Mitochondria-targeted triphenylphosphonium-based compounds inhibit FcεRI-dependent degranulation of mast cells by preventing mitochondrial dysfunction through Erk1/2
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Pavlyuchenkova, Anastasia N., Zinovkin, Roman A., Makievskaya, Ciara I., Galkin, Ivan I., and Chelombitko, Maria A.
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- 2022
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7. Mild depolarization of the inner mitochondrial membrane is a crucial component of an anti-aging program
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Vyssokikh, Mikhail Y., Holtze, Susanne, Averina, Olga A., Lyamzaev, Konstantin G., Panteleeva, Alisa A., Marey, Maria V., Zinovkin, Roman A., Severin, Fedor F., Skulachev, Maxim V., Fasel, Nicolas, Hildebrandt, Thomas B., and Skulachev, Vladimir P.
- Published
- 2020
8. Mitochondrial permeability transition pore is involved in oxidative burst and NETosis of human neutrophils
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Vorobjeva, Nina, Galkin, Ivan, Pletjushkina, Olga, Golyshev, Sergei, Zinovkin, Roman, Prikhodko, Anastasia, Pinegin, Vladimir, Kondratenko, Irina, Pinegin, Boris, and Chernyak, Boris
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- 2020
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9. Nuclear DNA as Predictor of Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Graft: A Pilot Study
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Likhvantsev, Valery V., Landoni, Giovanni, Grebenchikov, Oleg A., Skripkin, Yuri V., Zabelina, Tatiana S., Zinovkina, Liudmila A., Prikhodko, Anastasia S., Lomivorotov, Vladimir V., and Zinovkin, Roman A.
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- 2017
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10. Role of Mitochondria in the Regulation of Effector Functions of Granulocytes.
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Vorobjeva, Nina V., Chelombitko, Maria A., Sud'ina, Galina F., Zinovkin, Roman A., and Chernyak, Boris V.
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IMMUNE response ,WOUND healing ,GRANULOCYTES ,MITOCHONDRIA ,REACTIVE oxygen species ,EOSINOPHILS ,BASOPHILS - Abstract
Granulocytes (neutrophils, eosinophils, and basophils) are the most abundant circulating cells in the innate immune system. Circulating granulocytes, primarily neutrophils, can cross the endothelial barrier and activate various effector mechanisms to combat invasive pathogens. Eosinophils and basophils also play an important role in allergic reactions and antiparasitic defense. Granulocytes also regulate the immune response, wound healing, and tissue repair by releasing of various cytokines and lipid mediators. The effector mechanisms of granulocytes include the production of reactive oxygen species (ROS), degranulation, phagocytosis, and the formation of DNA-containing extracellular traps. Although all granulocytes are primarily glycolytic and have only a small number of mitochondria, a growing body of evidence suggests that mitochondria are involved in all effector functions as well as in the production of cytokines and lipid mediators and in apoptosis. It has been shown that the production of mitochondrial ROS controls signaling pathways that mediate the activation of granulocytes by various stimuli. In this review, we will briefly discuss the data on the role of mitochondria in the regulation of effector and other functions of granulocytes. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Penetrating cations induce pleiotropic drug resistance in yeast
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Galkina, Kseniia V., Besedina, Elizaveta G., Zinovkin, Roman A., Severin, Fedor F., and Knorre, Dmitry A.
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- 2018
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12. Editorial: Pharmacological Approaches Targeting Neutrophilic Inflammation
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Chernyak, Boris V., Sokolov, Alexey V., Hwang, Tsong-Long, Zinovkin, Roman A., and Sud’ina, Galina F.
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Pharmacology ,cancer-related inflammation ,Editorial ,neutrophils ,inflammation ,neutrophil extracellular traps (NETs) ,neutrophil-derived molecules - Published
- 2021
13. The Distinct Effects of the Mitochondria-Targeted STAT3 Inhibitors Mitocur-1 and Mitocur-3 on Mast Cell and Mitochondrial Functions.
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Pavlyuchenkova, Anastasia N., Chelombitko, Maria A., Fedorov, Artem V., Kuznetsova, Maria K., Zinovkin, Roman A., and Razin, Ehud
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CELL physiology ,STAT proteins ,MAST cells ,AMP-activated protein kinases ,ALLERGIES ,DRUG development - Abstract
There is accumulating evidence that mitochondria and mitochondrial STAT3 are involved in the activation of mast cells. The mitochondria-targeted curcuminoids Mitocur-1 and Mitocur-3 have been suggested to reduce antigen-dependent mast cell activation by inhibiting mitochondrial STAT3. The aim of the current work was to investigate the mechanisms of action of these mitocurcuminoids on mast cells and mitochondrial functions. The pretreatment of rat basophilic leukemia cells RBL-2H3 with Mitocur-1 and Mitocur-3 decreased antigen-dependent degranulation but did not affect spontaneous degranulation. Both compounds caused mitochondrial fragmentation and increased mitochondrial ROS. Inhibition of Drp1 prevented mitochondrial fragmentation induced by Mitocur-3 but not by Mitocur-1. The antioxidant N-acetylcysteine inhibited mitochondrial fission induced by Mitocur-1 but not Mitocur-3. Mitochondrial fragmentation caused by Mitocur-3 but not Mitocur-1 was accompanied by activation of Drp1 and AMPK. These data suggest a distinct mechanism of action of mitocurcuminoids on the mitochondria of RBL-2H3 cells: Mitocur-3 stimulated AMPK and caused Drp1-dependent mitochondrial fragmentation, while Mitocur-1-induced mitochondrial fission was ROS-dependent. This difference may contribute to the higher toxicity of Mitocur-3 compared to Mitocur-1. The findings contribute to further drug development for inflammatory and allergic diseases. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Altered Mitochondrial Morphology and Bioenergetics in a New Yeast Model Expressing Aβ42.
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Epremyan, Khoren K., Rogov, Anton G., Goleva, Tatyana N., Lavrushkina, Svetlana V., Zinovkin, Roman A., and Zvyagilskaya, Renata A.
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BIOENERGETICS ,MITOCHONDRIA ,ALZHEIMER'S disease ,CELL death ,YEAST ,MORPHOLOGY - Abstract
Alzheimer's disease (AD) is an incurable, age-related neurological disorder, the most common form of dementia. Considering that AD is a multifactorial complex disease, simplified experimental models are required for its analysis. For this purpose, genetically modified Yarrowia lipolytica yeast strains expressing Aβ42 (the main biomarker of AD), eGFP-Aβ42, Aβ40, and eGFP-Aβ40 were constructed and examined. In contrast to the cells expressing eGFP and eGFP-Aβ40, retaining "normal" mitochondrial reticulum, eGFP-Aβ42 cells possessed a disturbed mitochondrial reticulum with fragmented mitochondria; this was partially restored by preincubation with a mitochondria-targeted antioxidant SkQThy. Aβ42 expression also elevated ROS production and cell death; low concentrations of SkQThy mitigated these effects. Aβ42 expression caused mitochondrial dysfunction as inferred from a loose coupling of respiration and phosphorylation, the decreased level of ATP production, and the enhanced rate of hydrogen peroxide formation. Therefore, we have obtained the same results described for other AD models. Based on an analysis of these and earlier data, we suggest that the mitochondrial fragmentation might be a biomarker of the earliest preclinical stage of AD with an effective therapy based on mitochondria- targeted antioxidants. The simple yeast model constructed can be a useful platform for the rapid screening of such compounds. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Editorial: Pharmacological approaches targeting neutrophilic inflammation: Volume II.
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Sokolov, Alexey V., Chernyak, Boris V., Zinovkin, Roman A., Tsong-Long Hwang, and Sud'ina, Galina F.
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INFLAMMATION ,PHAGOCYTOSIS - Published
- 2022
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16. Mitochondria-Targeted Antioxidant SkQ1 Prevents the Development of Experimental Colitis in Mice and Impairment of the Barrier Function of the Intestinal Epithelium.
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Fedorov, Artem V., Chelombitko, Maria A., Chernyavskij, Daniil A., Galkin, Ivan I., Pletjushkina, Olga Yu., Vasilieva, Tamara V., Zinovkin, Roman A., and Chernyak, Boris V.
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INFLAMMATORY bowel diseases ,COLITIS ,ULCERATIVE colitis ,INTESTINES ,EPITHELIUM ,WEIGHT loss - Abstract
Mitochondria-targeted antioxidants have become promising candidates for the therapy of various pathologies. The mitochondria-targeted antioxidant SkQ1, which is a derivative of plastoquinone, has been successfully used in preclinical studies for the treatment of cardiovascular and renal diseases, and has demonstrated anti-inflammatory activity in a number of inflammatory disease models. The present work aimed to investigate the therapeutic potential of SkQ1 and C
12 TPP, the analog of SkQ1 lacking the antioxidant quinone moiety, in the prevention of sodium dextran sulfate (DSS) experimental colitis and impairment of the barrier function of the intestinal epithelium in mice. DSS-treated animals exhibited weight loss, bloody stool, dysfunction of the intestinal epithelium barrier (which was observed using FITC-dextran permeability), reduced colon length, and histopathological changes in the colon mucosa. SkQ1 prevented the development of clinical and histological changes in DSS-treated mice. SkQ1 also reduced mRNA expression of pro-inflammatory molecules TNF, IL-6, IL-1β, and ICAM-1 in the proximal colon compared with DSS-treated animals. SkQ1 prevented DSS-induced tight junction disassembly in Caco-2 cells. Pretreatment of mice by C12 TPP did not protect against DSS-induced colitis. Furthermore, C12 TPP did not prevent DSS-induced tight junction disassembly in Caco-2 cells. Our results suggest that SkQ1 may be a promising therapeutic agent for the treatment of inflammatory bowel diseases, in particular ulcerative colitis. [ABSTRACT FROM AUTHOR]- Published
- 2022
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17. The First Yarrowia lipolytica Yeast Models Expressing Hepatitis B Virus X Protein: Changes in Mitochondrial Morphology and Functions.
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Epremyan, Khoren K., Goleva, Tatyana N., Rogov, Anton G., Lavrushkina, Svetlana V., Zinovkin, Roman A., and Zvyagilskaya, Renata A.
- Abstract
Chronic hepatitis B virus infection is the dominant cause of hepatocellular carcinoma, the main cause of cancer death. HBx protein, a multifunctional protein, is essential for pathogenesis development; however, the underlying mechanisms are not fully understood. The complexity of the system itself, and the intricate interplay of many factors make it difficult to advance in understanding the mechanisms underlying these processes. The most obvious solution is to use simpler systems by reducing the number of interacting factors. Yeast cells are particularly suitable for studying the relationships between oxidative stress, mitochondrial dynamics (mitochondrial fusion and fragmentation), and mitochondrial dysfunction involved in HBx-mediated pathogenesis. For the first time, genetically modified yeast, Y. lipolytica, was created, expressing the hepatitis B virus core protein HBx, as well as a variant fused with eGFP at the C-end. It was found that cells expressing HBx experienced stronger oxidative stress than the control cells. Oxidative stress was alleviated by preincubation with the mitochondria-targeted antioxidant SkQThy. Consistent with these data, in contrast to the control cells (pZ-0) containing numerous mitochondrial forming a mitochondrial reticulum, in cells expressing HBx protein, mitochondria were fragmented, and preincubation with SkQThy partially restored the mitochondrial reticulum. Expression of HBx had a significant influence on the bioenergetic function of mitochondria, making them loosely coupled with decreased respiratory rate and reduced ATP formation. In sum, the first highly promising yeast model for studying the impact of HBx on bioenergy, redox-state, and dynamics of mitochondria in the cell and cross-talk between these parameters was offered. This fairly simple model can be used as a platform for rapid screening of potential therapeutic agents, mitigating the harmful effects of HBx. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria?
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Zorova, Ljubava D., Kovalchuk, Sergei I., Popkov, Vasily A., Chernikov, Valery P., Zharikova, Anastasia A., Khutornenko, Anastasia A., Zorov, Savva D., Plokhikh, Konstantin S., Zinovkin, Roman A., Evtushenko, Ekaterina A., Babenko, Valentina A., Pevzner, Irina B., Shevtsova, Yulia A., Goryunov, Kirill V., Plotnikov, Egor Y., Silachev, Denis N., Sukhikh, Gennady T., and Zorov, Dmitry B.
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MESENCHYMAL stem cells ,EXTRACELLULAR vesicles ,VESICLES (Cytology) ,MITOCHONDRIA ,MITOCHONDRIAL proteins ,OXYGEN consumption ,KREBS cycle ,MITOCHONDRIAL membranes - Abstract
Extracellular vesicles (EV) derived from stem cells have become an effective complement to the use in cell therapy of stem cells themselves, which has led to an explosion of research into the mechanisms of vesicle formation and their action. There is evidence demonstrating the presence of mitochondrial components in EV, but a definitive conclusion about whether EV contains fully functional mitochondria has not yet been made. In this study, two EV fractions derived from mesenchymal stromal stem cells (MSC) and separated by their size were examined. Flow cytometry revealed the presence of mitochondrial lipid components capable of interacting with mitochondrial dyes MitoTracker Green and 10-nonylacridine orange; however, the EV response to the probe for mitochondrial membrane potential was negative. Detailed analysis revealed components from all mitochondria compartments, including house-keeping mitochondria proteins and DNA as well as energy-related proteins such as membrane-localized proteins of complexes I, IV, and V, and soluble proteins from the Krebs cycle. When assessing the functional activity of mitochondria, high variability in oxygen consumption was noted, which was only partially attributed to mitochondrial respiratory activity. Our findings demonstrate that the EV contain all parts of mitochondria; however, their independent functionality inside EV has not been confirmed, which may be due either to the absence of necessary cofactors and/or the EV formation process and, probably the methodology of obtaining EV. [ABSTRACT FROM AUTHOR]
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- 2022
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19. Extrusion of mitochondria: Garbage clearance or cell–cell communication signals?
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Lyamzaev, Konstantin G., Zinovkin, Roman A., and Chernyak, Boris V.
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APOPTOSIS , *MESENCHYMAL stem cells , *ORGANIC wastes , *EXTRACELLULAR vesicles , *MITOCHONDRIA , *CELL death - Abstract
Mitochondria are dynamic organelles that regulate various intracellular signaling pathways, including the mechanisms of programmed cell death, differentiation, inflammation, and so on. Mitochondria may be extruded as membrane enveloped or as free organelles during developmental processes, inflammatory activation, and in the process of "garbage clearance" of damaged mitochondria in postmitotic cells. Extracellular mitochondria can be engulfed by immune and nonimmune cells and trigger intracellular signaling leading to an inflammatory response. At the same time, it was reported that the release of extracellular vesicles containing mitochondria from mesenchymal stem cells contributes to their therapeutic anti‐inflammatory effects. Numerous studies claim that engulfed mitochondria improve cellular bioenergetics, but this assumption requires further investigation. This review aims at a critical discussion of the mechanisms of mitochondrial extrusion in mammals, the reception of mitochondrial components, and the responses of recipient cells to extracellular mitochondria. [ABSTRACT FROM AUTHOR]
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- 2022
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20. Gene Expression Pattern of Peyer's Patch Lymphocytes Exposed to Kagocel Suggests Pattern-Recognition Receptors Mediate Its Action.
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Andreev-Andrievskiy, Alexander A., Zinovkin, Roman A., Mashkin, Mikhail A., Frolova, Olga Yu., Kazaishvili, Yuriy G., Scherbakova, Victoria S., Rudoy, Boris A., and Nesterenko, Vladimir G.
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GENE expression ,PATTERN perception receptors ,CONCANAVALIN A ,LYMPHOCYTES ,LYMPHOID tissue ,VIRUS diseases - Abstract
Kagocel is a synthetic carboxymethylcellulose derivative copolymerized with gossypol. Clinical data evidence its safety and efficiency for the treatment of flu and other viral infections via enhancement of interferon production. The gut-associated lymphoid tissue seems a likely site of kagocel action. The study was aimed to investigate the molecular mechanisms of its action using murine Peyer's patches lymphocytes as a test system and the cytokines production and gene expression patterns as the primary outcomes. The Peyer's patches lymphocytes isolated from BALB/c mice were stimulated with concanavalin A, or, to mimic viral infection, with a combination of concanavalin A and TLR3 ligand poly I:C. After 24 h of stimulation the cells were treated with saline, 30, 100, or 300 μg/ml of kagocel, or, as positive controls, 300 μg/ml oats b-D-glucan or 300 μg/ml lentinan. After 24 and 72 h of incubation with these drugs cytokines production was analyzed with ELISA and gene expression pattern was investigated using nCounter Inflammation panel chips followed by bioinformatics analysis. Expression of genes involved in the inflammatory response, antiviral defense, lymphocytes survival and proliferation (C1qa, C2, C3, Ccl21a, Il11, Il1b, Il23a, Il5, Ltb4r2, Alox15, Pla2g4a, Ptger1, Mapkapk5, Hras, Ifna1, Tlr2, Mrc1, Mx2) was upregulated in kagocel-treated Peyer's patches lymphocytes. A list of plausible transcription factors (CEBPs, IRF, NFκB, RXR, Stat, Tead4, and ZSCAN) and master-regulators has been identified (cIAP, CIKS, dock9, MEKK1, FXR, IKK, IRAK, TRAF, dsRNA:TLR3:TRIF). The changes in gene expression pattern and the outcomes of bioinformatics analysis suggest that pattern recognition receptors, TLRs and dectin-1, are the key mediators of kagocel immunomodulatory action, with the possible involvement of interferon autocrine loop. The genes upregulated with kagocel include diverse components of the innate immune defense system. [ABSTRACT FROM AUTHOR]
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- 2021
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21. Mitochondria as Targets for Endothelial Protection in COVID-19.
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Chernyak, Boris V., Popova, Ekaterina N., Zinovkina, Ludmila A., Lyamzaev, Konstantin G., and Zinovkin, Roman A.
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COVID-19 ,MITOCHONDRIA ,REACTIVE oxygen species ,CADHERINS ,VASCULAR cell adhesion molecule-1 - Published
- 2020
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22. Mitochondria-targeted triphenylphosphonium-based compounds do not affect estrogen receptor α.
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Zinovkina, Ludmila A., Galivondzhyan, Alina K., Prikhodko, Anastasia S., Galkin, Ivan I., and Zinovkin, Roman A.
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ESTROGEN receptors ,CELL cycle ,CELL proliferation ,CELL growth ,FLOW cytometry ,ESTROGEN - Abstract
Background. Targeting negatively charged mitochondria is often achieved using triphenylphosphonium (TPP) cations. These cationic vehicles may possess biological activity, and a docking study indicates that TPP-moieties may act as modulators of signaling through the estrogen receptor α (ERα). Moreover, in vivo and in vitro experiments revealed the estrogen-like effects of TPP-based compounds. Here, we tested the hypothesis that TPP-based compounds regulate the activity of ERα. Methods. We used ERa-positive and ERα-negative human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231, respectively). Cell proliferation was measured using a resazurin cell growth assay and a real-time cell analyzer assay. Cell cycle progression was analyzed using flow cytometry. Real-time PCR was used to assess mRNA expression of endogenous estrogen-responsive genes. Luciferase activity was measured to evaluate transcription driven by estrogen-responsive promoters in cells transfected with an estrogen response element (ERE)3-luciferase expression vector. Results. The TPP-based molecules SkQ1 and C12TPP, as well as the rhodamine-based SkQR1, did not increase the proliferation or alter the cell cycle progression of MCF- 7 cells. In contrast, 17β estradiol increased the proliferation of MCF-7 cells and the proportion of cells in the S/G2/M-phases of the cell cycle. TPP-based compounds did not affect the induction of transcription of an ERE-luciferase expression vector in vitro, and SkQ1 did not alter the levels of expression of estrogen-dependent genes encoding GREB1, TFF1, COX6, and IGFBP4. Conclusion. TPP-based compounds do not possess properties typical of ERα agonists. [ABSTRACT FROM AUTHOR]
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- 2020
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23. The 5′ untranslated region of Apaf-1 mRNA directs translation under apoptosis conditions via a 5′ end-dependent scanning mechanism
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Andreev, Dmitri E., Dmitriev, Sergey E., Zinovkin, Roman, Terenin, Ilya M., and Shatsky, Ivan N.
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- 2012
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24. Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice.
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Demyanenko, Ilya A., Zakharova, Vlada V., Ilyinskaya, Olga P., Vasilieva, Tamara V., Fedorov, Artem V., Manskikh, Vasily N., Zinovkin, Roman A., Pletjushkina, Olga Yu, Chernyak, Boris V., Skulachev, Vladimir P., and Popova, Ekaterina N.
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- 2017
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25. Mitochondria-Targeted Antioxidants and Uncouplers of Oxidative Phosphorylation in Treatment of the Systemic Inflammatory Response Syndrome (SIRS).
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Zakharova, Vlada V., Pletjushkina, Olga Yu., Zinovkin, Roman A., Popova, Ekaterina N., and Chernyak, Boris V.
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SYSTEMIC inflammatory response syndrome ,OXIDATIVE phosphorylation ,SHOCK (Pathology) ,MITOCHONDRIA ,ANTIOXIDANT analysis - Abstract
Systemic inflammatory response syndrome (SIRS) development is accompanied by mitochondrial dysfunction and excessive ROS production. Mitochondrial dysfunctions also occur in many SIRS-related diseases and may be critical for their pathogenesis; therefore, a use of mitochondria-targeted drugs is a promising trend in SIRS research and therapy. Here, we review recent studies concerning the application of the mitochondria-targeted antioxidants and uncouplers of oxidative phosphorylation in animal models of SIRS and related diseases. We propose that a new class of uncouplers of oxidative phosphorylation, lipophilic cations could be a base for a new generation of drugs for SIRS treatment. J. Cell. Physiol. 232: 904-912, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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26. RNA-dependent disassembly of nuclear bodies.
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Musinova, Yana R., Lisitsyna, Olga M., Sorokin, Dmitry V., Arifulin, Eugene A., Smirnova, Tatiana A., Zinovkin, Roman A., Potashnikova, Daria M., Vassetzky, Yegor S., and Sheval, Eugene V.
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INTERPHASE ,GENOMES ,RNA analysis - Abstract
Nuclear bodies are membraneless organelles that play important roles in genome functioning. A specific type of nuclear bodies known as interphase prenucleolar bodies (iPNBs) are formed in the nucleoplasm after hypotonic stress from partially disassembled nucleoli. iPNBs are then disassembled, and the nucleoli are reformed simultaneously. Here, we show that diffusion of B23 molecules (also known as nucleophosmin, NPM1) from iPNBs, but not fusion of iPNBs with the nucleoli, contributes to the transfer of B23 from iPNBs to the nucleoli. Maturation of pre-ribosomal RNAs (rRNAs) and the subsequent outflow of mature rRNAs from iPNBs led to the disassembly of iPNBs. We found that B23 transfer was dependent on the synthesis of pre-rRNA molecules in nucleoli; these pre-rRNA molecules interacted with B23 and led to its accumulation within nucleoli. The transfer of B23 between iPNBs and nucleoli was accomplished through a nucleoplasmic pool of B23, and increased nucleoplasmic B23 content retarded disassembly, whereas B23 depletion accelerated disassembly. Our results suggest that iPNB disassembly and nucleolus assembly might be coupled through RNA-dependent exchange of nucleolar proteins, creating a highly dynamic system with long-distance correlations between spatially distinct processes. [ABSTRACT FROM AUTHOR]
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- 2016
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27. Efficacy of Mitochondrial Antioxidant Plastoquinonyl-decyl-triphenylphosphonium Bromide (SkQ1) in the Rat Model of Autoimmune Arthritis.
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Andreev-Andrievskiy, Alexander A., Kolosova, Nataliya G., Stefanova, Natalia A., Lovat, Maxim V., Egorov, Maxim V., Manskikh, Vasily N., Zinovkin, Roman A., Galkin, Ivan I., Prikhodko, Anastasia S., Skulachev, Maxim V., and Lukashev, Alexander N.
- Published
- 2016
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28. Methanol May Function as a Cross-Kingdom Signal.
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Dorokhov, Yuri L., Komarova, Tatiana V., Petrunia, Igor V., Kosorukov, Vyacheslav S., Zinovkin, Roman A., Shindyapina, Anastasia V., Frolova, Olga Y., and Gleba, Yuri Y.
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PECTINESTERASE ,MESSENGER RNA ,FORMALDEHYDE ,ALCOHOL dehydrogenase ,ZINC enzymes ,CLONE cells ,CELL culture - Abstract
Recently, we demonstrated that leaf wounding results in the synthesis of pectin methylesterase (PME), which causes the plant to release methanol into the air. Methanol emitted by a wounded plant increases the accumulation of methanol-inducible gene mRNA and enhances antibacterial resistance as well as cell-to-cell communication, which facilitates virus spreading in neighboring plants. We concluded that methanol is a signaling molecule involved in within-plant and plant-to-plant communication. Methanol is considered to be a poison in humans because of the alcohol dehydrogenase (ADH)-mediated conversion of methanol into toxic formaldehyde. However, recent data showed that methanol is a natural compound in normal, healthy humans. These data call into question whether human methanol is a metabolic waste product or whether methanol has specific function in humans. Here, to reveal human methanol-responsive genes (MRGs), we used suppression subtractive hybridization cDNA libraries of HeLa cells lacking ADH and exposed to methanol. This design allowed us to exclude genes involved in formaldehyde and formic acid detoxification from our analysis. We identified MRGs and revealed a correlation between increases in methanol content in the plasma and changes in human leukocyte MRG mRNA levels after fresh salad consumption by volunteers. Subsequently, we showed that the methanol generated by the pectin/PME complex in the gastrointestinal tract of mice induces the up- and downregulation of brain MRG mRNA. We used an adapted Y-maze to measure the locomotor behavior of the mice while breathing wounded plant vapors in two-choice assays. We showed that mice prefer the odor of methanol to other plant volatiles and that methanol changed MRG mRNA accumulation in the mouse brain. We hypothesize that the methanol emitted by wounded plants may have a role in plant-animal signaling. The known positive effect of plant food intake on human health suggests a role for physiological methanol in human gene regulation. [ABSTRACT FROM AUTHOR]
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- 2012
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29. Corrigendum: The Role Played by Mitochondria in FcϵRI-Dependent Mast Cell Activation.
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Chelombitko, Maria A., Chernyak, Boris V., Fedorov, Artem V., Zinovkin, Roman A., Razin, Ehud, and Paruchuru, Lakhsmi Bhargavi
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MAST cells ,MITOCHONDRIA - Abstract
Corrigendum: The Role Played by Mitochondria in Fc RI-Dependent Mast Cell Activation. Mast cell, mitochondria, Fc RI-dependent activation, IgE, allergy. [Extracted from the article]
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- 2020
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30. Mitochondrial reactive oxygen species are involved in chemoattractant-induced oxidative burst and degranulation of human neutrophils in vitro.
- Author
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Vorobjeva, Nina, Prikhodko, Anastasia, Galkin, Ivan, Pletjushkina, Olga, Zinovkin, Roman, Sud’ina, Galina, Chernyak, Boris, and Pinegin, Boris
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NEUTROPHILS , *CHEMOTAXIS , *REACTIVE oxygen species , *OXIDATIVE stress , *NICOTINAMIDE adenine dinucleotide phosphate , *APOPTOSIS , *IN vitro studies , *PHYSIOLOGY - Abstract
Activation of neutrophils is accompanied by the oxidative burst, exocytosis of various granule types (degranulation) and a delay in spontaneous apoptosis. The major source of reactive oxygen species (ROS) in human neutrophils is NADPH oxidase (NOX2), however, other sources of ROS also exist. Although the function of ROS is mainly defensive, they can also play a regulatory role in cell signaling. However, the contribution of various sources of ROS in these processes is not clear. We investigated a possible role of mitochondria-derived ROS (mtROS) in the regulation of neutrophil activation induced by chemoattractant fMLP in vitro . Using the mitochondria-targeted antioxidant SkQ1, we demonstrated that mtROS are implicated in the oxidative burst caused by NOX2 activation as well as in the exocytosis of primary (azurophil) and secondary (specific) granules. Scavenging of mtROS with SkQ1 slightly accelerated spontaneous apoptosis and significantly stimulated apoptosis of fMLP-activated neutrophils. These data indicate that mtROS play a critical role in signal transduction that mediates the major neutrophil functional responses in the process of activation. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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31. Low concentration of uncouplers of oxidative phosphorylation decreases the TNF-induced endothelial permeability and lethality in mice.
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Zakharova, Vlada V., Pletjushkina, Olga Yu., Galkin, Ivan I., Zinovkin, Roman A., Chernyak, Boris V., Krysko, Dmitri V., Bachert, Claus, Krysko, Olga, Skulachev, Vladimir P., and Popova, Ekaterina N.
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OXIDATIVE phosphorylation , *TUMOR necrosis factors , *ENDOTHELIAL cells , *PERMEABILITY (Biology) , *LABORATORY mice , *MITOCHONDRIAL pathology - Abstract
Mitochondrial dysfunctions occur in many diseases linked to the systemic inflammatory response syndrome (SIRS). Mild uncoupling of oxidative phosphorylation is known to rescue model animals from pathologies related to mitochondrial dysfunctions and overproduction of reactive oxygen species (ROS). To study the potential of SIRS therapy by uncoupling, we tested protonophore dinitrophenol (DNP) and a free fatty acid (FFA) anion carrier, lipophilic cation dodecyltriphenylphosphonium (C 12 TPP) in mice and in vitro models of SIRS. DNP and C 12 TPP prevented the body temperature drop and lethality in mice injected with high doses of a SIRS inducer, tumor necrosis factor (TNF). The mitochondria-targeted antioxidant plastoquinonyl decyltriphenylphosphonium (SkQ1) which also catalyzes FFA-dependent uncoupling revealed similar protective effects and downregulated expression of the NFκB-regulated genes (VCAM1, ICAM1, MCP1, and IL-6) involved in the inflammatory response of endothelium in aortas of the TNF-treated mice. In vitro mild uncoupling rescued from TNF-induced endothelial permeability, disassembly of cell contacts and VE-cadherin cleavage by the matrix metalloprotease 9 (ММР9). The uncouplers prevented TNF-induced expression of MMP9 via inhibition of NFκB signaling. Water-soluble antioxidant Trolox also prevented TNF-induced activation and permeability of endothelium in vitro via inhibition of NFκB signaling, suggesting that the protective action of the uncouplers is linked to their antioxidant potential. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
32. The effect of betaq259l mutation on MgADP-inhibition of B. subtilis H+-FOF1-ATP-synthase.
- Author
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Lapashina, Anna, Vitushkina, Maria, Zinovkin, Roman, and Feniouk, Boris
- Published
- 2014
- Full Text
- View/download PDF
33. Synthetic fragment (60–76) of RAGE improves brain mitochondria function in olfactory bulbectomized mice.
- Author
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Avetisyan, Armine, Balasanyants, Samson, Simonyan, Ruben, Koroev, Dmitriy, Kamynina, Anna, Zinovkin, Roman, Bobkova, Natalia, and Volpina, Olga
- Subjects
- *
ADVANCED glycation end-products , *OLFACTORY perception , *RECEPTOR for advanced glycation end products (RAGE) , *THETA rhythm , *ANGER , *MATHEMATICAL complexes , *TREATMENT effectiveness - Abstract
The receptor for advanced glycation end products (RAGE) is considered to contribute to the pathogenesis of Alzheimer's disease (AD), mediating amyloid beta (Aβ) accumulation, mitochondrial damage, and neuroinflammation. Previously, we have synthesized small peptides corresponding to the fragments (60–76) (P1) and (60–62) (P2) of the RAGE extracellular domain, and have shown that administration of P1 fragment but not P2 results in restoration of the spatial memory and decreases the brain Aβ (1–40) level in olfactory bulbectomized (OBX) mice demonstrating main features of Alzheimer's type neurodegeneration. In the present study, we have investigated the supposed mechanism of the therapeutic efficacy of P1 RAGE fragment and compared it to P2 short fragment. We have found that P1 restored activities of the respiratory chain in the Complexes I and IV in both cortical and hippocampal mitochondria of the OBX mice while P2 had no effect. Besides, fluorescein-labeled analog Flu-P1 bound to Aβ (1–40) and Aβ (1–42) with high affinity (K d in the nanomolar range) whereas Flu-P2 revealed low affinity with tenfold higher K d value for Aβ (1–40) and did not bind to Aβ (1–42). However, neither of the peptides had a notable impact on inflammation, estimated as mRNA expression of proinflammatory cytokines in the brain tissues of OBX mice. Taken together, our results suggest that direct Aβ-P1 interaction is one of the molecular events mediating the protection of the mitochondria in OBX animals from Aβ toxic effect. The RAGE fragment P1 would be the soluble decoy for Aβs and serve as a promising therapeutic agent against neurodegeneration accompanied by mitochondrial dysfunction. • Peptide fragment (60–76) of RAGE restored activities of the respiratory chain Complexes I and IV in -mitochondria of OBX mice. • Fluorescein-labeled analog Flu-(60–76) bound to Aβ peptides (1–40)/(1–42) with a high affinity, K d is in the nanomolar range. • The RAGE fragment (60–76) would be the soluble decoy for Aβs and serve as a promising therapeutic agent. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
34. Mitochondria-targeted antioxidants prevent TNFα induced endothelial cell damage.
- Author
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Zakharova, Vlada, Galkin, Ivan, Olga Pletjushkina, Valerya Romashchenko, Chernyak, Boris, Zinovkin, Roman, Popova, Ekaterina, and Skulachev, Vladimir
- Subjects
- *
PHYSIOLOGICAL effects of antioxidants , *TUMOR necrosis factors , *APOPTOSIS inhibition - Abstract
Using mitochondria-targeted antioxidants made of plastoquinone and penetrating cations (SkQ family), we investigated the role of mitochondrial reactive oxygen species (ROS) in the TNF-induced cytoskeleton reorganization and apoptosis in endothelial cells. SkQ, as well as the classic antioxidant N-acetylcysteine and Trolox significantly suppressed apoptosis induced by TNF [1]. Their action was directed at the suppressing the release of cytochrome c. We showed that SkQ treatment led to an increased level of Bcl-2, and reduced levels of Bax and p53 [1]. Nevertheless, SkQ had no on Bcl-2 mRNA expression, but it enhances Bcl-2 phosphorylation thus contributing to the inhibition of protein ubiquitination. We have also shown that SkQ prevents Bcl-2 proteolysis induced by TNF. We assume that SkQ may affect activation of the redox sensitive stress kinases that are involved in the phosphorylation of the Bcl-2 family proteins. In our system we plan to evaluate the influence of mitochondria-targeted antioxidants on DNA damage induced by TNF. The results will be presented at the conference. We showed that SkQ as well as N-acetylcysteine and Trolox inhibited TNF-induced monolayer endothelial permeability for dextran with a molecular weight of 65-85 kDa. Endothelial monolayer permeability induced by TNF is accompanied by cytoskeleton reorganization. We observed that SkQ prevented TNF -induced release of VE-cadherin and β-catenin from the contact area, as well as disassembly of the annular peripheral beam of actin microfilaments. TNF-activated matrix metalloproteinases (MMP) cleaved extracellular fragment of VE-cadherins. We observed MMP-dependent decrease in the overall VE-cadherin level in the cells and the appearance of its cleavage product in cell medium induced by TNF. These effects were markedly suppressed by SkQ. Thus, it was shown that TNF-dependent endothelial cell damage was largely dependent on ROS production in mitochondria, thus indicating promising angioprotective action of SkQ. [ABSTRACT FROM AUTHOR]
- Published
- 2015
35. Mitochondria-targeted antioxidants prevent TNFα induced endothelial cell damage.
- Author
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Zakharova, Vlada, Galkin, Ivan, Pletjushkina, Olga, Chernyak, Boris, Zinovkin, Roman, Popova, Ekaterina, and Skulachev, Vladimir
- Published
- 2014
- Full Text
- View/download PDF
36. The role of residue beta249 in MgADP inhibition of Escherichia coli ATP synthase.
- Author
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Feniouk, Boris, Prikhodko, Anastasia, Lapashina, Anna, Vitushkina, Maria, and Zinovkin, Roman
- Published
- 2014
- Full Text
- View/download PDF
37. Mitochondria-targeted Uncouplers Decrease Inflammatory Reactions in Endothelial Cells by Enhancing Methylation of the ICAM1 Gene Promoter.
- Author
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Zinovkina LA, Makievskaya CI, Galkin II, and Zinovkin RA
- Subjects
- Humans, Inflammation metabolism, DNA Methylation, Anti-Inflammatory Agents pharmacology, DNA metabolism, DNA pharmacology, RNA, Messenger metabolism, Intercellular Adhesion Molecule-1 genetics, Intercellular Adhesion Molecule-1 metabolism, Intercellular Adhesion Molecule-1 pharmacology, Endothelial Cells metabolism, Mitochondria metabolism
- Abstract
Introduction: The study aimed to investigate the effects of low concentrations of mitochondrial uncouplers in endothelial cells on the CpG dinucleotide methylation of the ICAM1 gene promoter. The excessive inflammatory response in the endothelium is responsible for the development of many cardiovascular diseases. Mitochondria are important regulators of endothelial cell functions. Mild uncoupling of oxidative phosphorylation and respiration in endothelial mitochondria exerts a long lasting anti-inflammatory effect. However, the detailed mechanism of the anti-inflammatory activity of mitochondrial uncouplers remains unclear.We hypothesized that mild mitochondrial uncoupling leads to epigenetic changes in genomic DNA contributing to the anti-inflammatory response., Methods: We studied the long-term effects of mitochondria-targeted compounds with the uncoupler's activities: the antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1), dodecyl-triphenylphosphonium (C12TPP), and 2,4-dinitrophenol (DNP). The mRNA expression of the intercellular adhesion molecule 1 (ICAM1), a marker of inflammatory activation of endothelial cells, was measured by RT-qPCR. Cytosine methylation in the CpG sites of the ICAM1 gene promoter was estimated by bisulfite sequencing of individual clones., Results: It was found that downregulation of ICAM1 expression caused by DNP and C12TPP was accompanied by an increase in the methylation of CpG sites in the ICAM1 gene promoter. None of the compounds affected intracellular or intramitochondrial ATP levels., Conclusion: Low concentrations of mitochondrial oxidative phosphorylation uncouplers are able to increase methylation of ICAM1 gene promoter, which corresponds to the observed decrease in the levels of mRNA of this gene. Thus, the change in methylation of the ICAM1 gene promoter may underlie the mechanism of decreased ICAM1 expression caused by mild mitochondrial depolarization. Mitochondrial uncouplers may be exploited as possible therapeutic candidates to treat excessive inflammation in endothelium, by changing the methylation status of genomic DNA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
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- View/download PDF
38. Current perspectives of mitochondria-targeted antioxidants in cancer prevention and treatment.
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Zinovkin RA, Lyamzaev KG, and Chernyak BV
- Abstract
Oxidative stress nearly always accompanies all stages of cancer development. At the early stages, antioxidants may help to reduce reactive oxygen species (ROS) production and exhibit anticarcinogenic effects. In the later stages, ROS involvement becomes more complex. On the one hand, ROS are necessary for cancer progression and epithelial-mesenchymal transition. On the other hand, antioxidants may promote cancer cell survival and may increase metastatic frequency. The role of mitochondrial ROS in cancer development remains largely unknown. This paper reviews experimental data on the effects of both endogenous and exogenous antioxidants on cancerogenesis focusing on the development and application of mitochondria-targeted antioxidants. We also discuss the prospects for antioxidant cancer therapy, focusing on the use of mitochondria-targeted antioxidants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zinovkin, Lyamzaev and Chernyak.)
- Published
- 2023
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- View/download PDF
39. The Role Played by Mitochondria in FcεRI-Dependent Mast Cell Activation.
- Author
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Chelombitko MA, Chernyak BV, Fedorov AV, Zinovkin RA, Razin E, and Paruchuru LB
- Subjects
- Animals, Calcium metabolism, Humans, Immunoglobulin E metabolism, Microphthalmia-Associated Transcription Factor metabolism, Signal Transduction physiology, Mast Cells metabolism, Mast Cells physiology, Mitochondria metabolism, Mitochondria physiology, Receptors, IgE metabolism
- Abstract
Mast cells play a key role in the regulation of innate and adaptive immunity and are involved in pathogenesis of many inflammatory and allergic diseases. The most studied mechanism of mast cell activation is mediated by the interaction of antigens with immunoglobulin E (IgE) and a subsequent binding with the high-affinity receptor Fc epsilon RI (FcεRI). Increasing evidences indicated that mitochondria are actively involved in the FcεRI-dependent activation of this type of cells. Here, we discuss changes in energy metabolism and mitochondrial dynamics during IgE-antigen stimulation of mast cells. We reviewed the recent data with regards to the role played by mitochondrial membrane potential, mitochondrial calcium ions (Ca
2+ ) influx and reactive oxygen species (ROS) in mast cell FcεRI-dependent activation. Additionally, in the present review we have discussed the crucial role played by the pyruvate dehydrogenase (PDH) complex, transcription factors signal transducer and activator of transcription 3 (STAT3) and microphthalmia-associated transcription factor (MITF) in the development and function of mast cells. These two transcription factors besides their nuclear localization were also found to translocate in to the mitochondria and functions as direct modulators of mitochondrial activity. Studying the role played by mast cell mitochondria following their activation is essential for expanding our basic knowledge about mast cell physiological functions and would help to design mitochondria-targeted anti-allergic and anti-inflammatory drugs., (Copyright © 2020 Chelombitko, Chernyak, Fedorov, Zinovkin, Razin and Paruchuru.)- Published
- 2020
- Full Text
- View/download PDF
40. Mitochondria-Targeted Drugs.
- Author
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Zinovkin RA and Zamyatnin AA
- Subjects
- Animals, Antioxidants pharmacokinetics, Antioxidants therapeutic use, Humans, Mitochondria drug effects, Mitochondria pathology, Organophosphorus Compounds pharmacokinetics, Organophosphorus Compounds therapeutic use, Oxidative Stress drug effects, Plastoquinone administration & dosage, Plastoquinone pharmacokinetics, Plastoquinone therapeutic use, Reactive Oxygen Species metabolism, Ubiquinone administration & dosage, Ubiquinone pharmacokinetics, Ubiquinone therapeutic use, Antioxidants administration & dosage, Drug Delivery Systems methods, Mitochondria metabolism, Organophosphorus Compounds administration & dosage, Plastoquinone analogs & derivatives, Ubiquinone analogs & derivatives
- Abstract
Background: Targeting of drugs to the subcellular compartments represents one of the modern trends in molecular pharmacology. The approach for targeting mitochondria was developed nearly 50 years ago, but only in the last decade has it started to become widely used for delivering drugs. A number of pathologies are associated with mitochondrial dysfunction, including cardiovascular, neurological, inflammatory and metabolic conditions., Objective: This mini-review aims to highlight the role of mitochondria in pathophysiological conditions and diseases, to classify and summarize our knowledge about targeting mitochondria and to review the most important preclinical and clinical data relating to the antioxidant lipophilic cations MitoQ and SkQ1., Methods: This is a review of available information in the PubMed and Clinical Trials databases (US National Library of Medicine) with no limiting period., Results and Conclusion: Mitochondria play an important role in the pathogenesis of many diseases and possibly in aging. Both MitoQ and SkQ1 have shown many beneficial features in animal models and in a few completed clinical trials. More clinical trials and research efforts are needed to understand the signaling pathways influenced by these compounds. The antioxidant lipophilic cations have great potential for the treatment of a wide range of pathologies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2019
- Full Text
- View/download PDF
41. Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice.
- Author
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Demyanenko IA, Popova EN, Zakharova VV, Ilyinskaya OP, Vasilieva TV, Romashchenko VP, Fedorov AV, Manskikh VN, Skulachev MV, Zinovkin RA, Pletjushkina OY, Skulachev VP, and Chernyak BV
- Subjects
- Aging, Animals, Cadherins metabolism, Cell Movement drug effects, Cytokines metabolism, Epithelium growth & development, Epithelium metabolism, Extracellular Matrix Proteins biosynthesis, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Myofibroblasts metabolism, Plastoquinone pharmacology, Reactive Oxygen Species metabolism, Skin injuries, Transforming Growth Factor beta pharmacology, Antioxidants pharmacology, Mitochondria drug effects, Plastoquinone analogs & derivatives, Wound Healing drug effects
- Abstract
The process of skin wound healing is delayed or impaired in aging animals. To investigate the possible role of mitochondrial reactive oxygen species (mtROS) in cutaneous wound healing of aged mice, we have applied the mitochondria-targeted antioxidant SkQ1. The SkQ1 treatment resulted in accelerated resolution of the inflammatory phase, formation of granulation tissue, vascularization and epithelization of the wounds. The wounds of SkQ1-treated mice contained increased amount of myofibroblasts which produce extracellular matrix proteins and growth factors mediating granulation tissue formation. This effect resembled SkQ1-induced differentiation of fibroblasts to myofibroblast, observed earlierin vitro. The Transforming Growth Factor beta (TGFb) produced by SkQ1-treated fibroblasts was found to stimulated motility of endothelial cells in vitro, an effect which may underlie pro-angiogenic action of SkQ1 in the wounds. In vitro experiments showed that SkQ1 prevented decomposition of VE-cadherin containing contacts and following increase in permeability of endothelial cells monolayer, induced by pro-inflammatory cytokine TNF. Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1. Our findings point to an important role of mtROS in pathogenesis of age-related chronic wounds.
- Published
- 2015
- Full Text
- View/download PDF
42. Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium.
- Author
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Zinovkin RA, Romaschenko VP, Galkin II, Zakharova VV, Pletjushkina OY, Chernyak BV, and Popova EN
- Subjects
- Animals, Antioxidants pharmacology, Aorta drug effects, Aorta metabolism, Endothelial Cells drug effects, Endothelial Cells metabolism, Endothelium, Vascular drug effects, Intercellular Adhesion Molecule-1 metabolism, Interleukin-6 blood, Mice, Mitochondria drug effects, NF-kappa B metabolism, Phosphorylation drug effects, Plastoquinone analogs & derivatives, Plastoquinone pharmacology, Tumor Necrosis Factor-alpha blood, Aging metabolism, Endothelium, Vascular metabolism, Inflammation metabolism, Mitochondria metabolism, Reactive Oxygen Species metabolism
- Abstract
Vascular aging is accompanied by increases in circulatory proinflammatory cytokines leading to inflammatory endothelial response implicated in early atherogenesis. To study the possible role of mitochondria-derived reactive oxygen species (ROS) in this phenomenon, we applied the effective mitochondria-targeted antioxidant SkQ1, the conjugate of plastoquinone with dodecyltriphenylphosphonium. Eight months treatment of (CBAxC57BL/6) F1 mice with SkQ1 did not prevent age-related elevation of the major proinflammatory cytokines TNF and IL-6 in serum, but completely abrogated the increase in adhesion molecule ICAM1 expression in aortas of 24-month-old animals. In endothelial cell culture, SkQ1 also attenuated TNF-induced increase in ICAM1, VCAM, and E-selectin expression and secretion of IL-6 and IL-8, and prevented neutrophil adhesion to the endothelial monolayer. Using specific inhibitors to transcription factor NF-κB and stress-kinases p38 and JNK, we demonstrated that TNF-induced ICAM1 expression depends mainly on NF-κB activity and, to a lesser extent, on p38. SkQ1 had no effect on p38 phosphorylation (activation) but significantly reduced NF-κB activation by inhibiting phosphorylation and proteolytic cleavage of the inhibitory subunit IκBα. The data indicate an important role of mitochondrial reactive oxygen species in regulation of the NF-κB pathway and corresponding age-related inflammatory activation of endothelium.
- Published
- 2014
- Full Text
- View/download PDF
43. Processing and subcellular localization of the leader papain-like proteinase of Beet yellows closterovirus.
- Author
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Zinovkin RA, Erokhina TN, Lesemann DE, Jelkmann W, and Agranovsky AA
- Subjects
- Aizoaceae virology, Amino Acid Sequence, Antibodies, Monoclonal, Cells, Cultured, Closterovirus genetics, Microscopy, Electron, Papain chemistry, Recombinant Fusion Proteins, Serine Endopeptidases chemistry, Beta vulgaris virology, Closterovirus enzymology, Membrane Proteins, Papain metabolism, Serine Endopeptidases metabolism, Subcellular Fractions enzymology
- Abstract
ORF 1a of Beet yellows closterovirus (BYV) encodes the domains of the papain-like proteinase (PCP), methyltransferase (MT) and RNA helicase. BYV cDNA inserts encoding the PCP-MT region were cloned in pGEX vectors next to the glutathione S-transferase gene (GST). In a 'double tag' construct, the GST-PCP-MT cDNA was flanked by the 3'-terminal six histidine triplets. Following expression in E. coli, the fusion proteins were specifically self-cleaved into the GST-PCP and MT fragments. MT-His(6) was purified on Ni-NTA agarose and its N-terminal sequence determined by Edman degradation as GVEEEA, thus providing direct evidence for the Gly(588)/Gly(589) bond cleavage. The GST-PCP fragment purified on glutathione S-agarose was used as an immunogen to produce anti-PCP monoclonal antibodies (mAbs). On Western blots of proteins from virus-infected Tetragonia expansa, the mAbs recognized the 66 kDa protein. Immunogold labelling of BYV-infected tissue clearly indicated association of the PCP with the BYV-induced membranous vesicle aggregates, structures related to closterovirus replication.
- Published
- 2003
- Full Text
- View/download PDF
44. Ultrastructural localization and epitope mapping of the methyltransferase-like and helicase-like proteins of Beet yellows virus.
- Author
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Erokhina TN, Vitushkina MV, Zinovkin RA, Lesemann DE, Jelkmann W, Koonin EV, and Agranovsky AA
- Subjects
- Amino Acid Sequence, Antibodies, Monoclonal immunology, Binding Sites, Cell Membrane virology, Cytoplasmic Vesicles virology, Epitopes immunology, Epitopes isolation & purification, Immunohistochemistry, Methyltransferases immunology, Molecular Sequence Data, Plant Leaves virology, Plants ultrastructure, RNA Helicases immunology, Sequence Alignment, Closterovirus enzymology, Methyltransferases isolation & purification, Plants virology, RNA Helicases isolation & purification
- Abstract
Monoclonal antibodies (MAbs) specific to the methyltransferase (MT) and helicase (HEL) domains of the closterovirus Beet yellows virus (BYV) were used for immunogold labelling of ultrathin sections of virus-infected Tetragonia expansa plants. MAbs 4A2 and 4A5 from the MT panel, and 1C4 from the HEL panel, specifically labelled distinct closterovirus-induced membranous structures, the 'BYV-type vesicles', thus suggesting that the closterovirus MT-like and HEL-like proteins co-localize in these structures. Probing of the MT and HEL MAbs with synthetic octapeptides spanning the sequences of the recombinant MT and HEL fragments that had been used as immunogens showed that 4A5 and 4A2 recognized a single epitope, SRLLENET (aa 686-692 in the BYV 1a protein), and 1C4 reacted with the DDPF epitope (aa 2493-2496). These epitopes apparently reside on the exposed parts of the membrane-associated molecules of the closterovirus MT-like and HEL-like proteins. Two other epitopes determined for the MT MAbs that were nonreactive in the immunogold labelling, namely TMVTPGEL (aa 750-757; MAbs 3C5, 4B4 and 4C5) and SREQLVEA (aa 806-813; MAb 2A4), are possibly buried in the MT domain fold or shielded by membranes or other proteins involved in the viral replicative complex.
- Published
- 2001
- Full Text
- View/download PDF
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