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  1. Article ; Online: Innate Immunity and Phenoptosis.

    Chernyak, Boris V / Lyamzaev, Konstantin G

    Biochemistry. Biokhimiia

    2023  Volume 87, Issue 12, Page(s) 1634–1639

    Abstract: The hypothesis is proposed that activation of innate immunity is the primary mechanism of phenoptosis (programmed death of an organism). In support of the hypothesis, we discuss (i) the data on active release of signaling molecules from the cell ... ...

    Abstract The hypothesis is proposed that activation of innate immunity is the primary mechanism of phenoptosis (programmed death of an organism). In support of the hypothesis, we discuss (i) the data on active release of signaling molecules from the cell producing excessive inflammation; (ii) the data on contribution of mitochondrial production of reactive oxygen species to immune response.
    MeSH term(s) Humans ; Immunity, Innate ; Inflammation ; Signal Transduction ; Mitochondria
    Language English
    Publishing date 2023-01-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297922120185
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    In stock of ZB MED Cologne/Königswinter

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  2. Article: Current perspectives of mitochondria-targeted antioxidants in cancer prevention and treatment.

    Zinovkin, Roman A / Lyamzaev, Konstantin G / Chernyak, Boris V

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1048177

    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 ... ...

    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.
    Language English
    Publishing date 2023-03-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1048177
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  3. Article ; Online: Extrusion of mitochondria: Garbage clearance or cell-cell communication signals?

    Lyamzaev, Konstantin G / Zinovkin, Roman A / Chernyak, Boris V

    Journal of cellular physiology

    2022  Volume 237, Issue 5, Page(s) 2345–2356

    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 ... ...

    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.
    MeSH term(s) Animals ; Cell Communication ; Inflammation/metabolism ; Mammals ; Mitochondria/metabolism ; Mitophagy/physiology ; Organelles/metabolism
    Language English
    Publishing date 2022-03-06
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 3116-1
    ISSN 1097-4652 ; 0021-9541
    ISSN (online) 1097-4652
    ISSN 0021-9541
    DOI 10.1002/jcp.30711
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  4. Article: The critical role of mitochondrial lipid peroxidation in ferroptosis: insights from recent studies.

    Lyamzaev, Konstantin G / Panteleeva, Alisa A / Simonyan, Ruben A / Avetisyan, Armine V / Chernyak, Boris V

    Biophysical reviews

    2023  Volume 15, Issue 5, Page(s) 875–885

    Abstract: Ferroptosis is a regulated form of necrotic cell death reliant on iron-catalyzed lipid peroxidation. Although the precise involvement of mitochondria in ferroptosis remains incompletely elucidated, recent research indicates that mitochondrial oxidative ... ...

    Abstract Ferroptosis is a regulated form of necrotic cell death reliant on iron-catalyzed lipid peroxidation. Although the precise involvement of mitochondria in ferroptosis remains incompletely elucidated, recent research indicates that mitochondrial oxidative events wield a pivotal influence in this mechanism. This article centers on the most recent discoveries, spotlighting the significance of mitochondrial lipid peroxidation in the occurrence of ferroptosis. Modern investigative tools, such as mitochondria-specific dyes responsive to lipid peroxidation and antioxidants targeting mitochondria, have been employed to delve into this phenomenon. The authors' recent empirical evidence demonstrates that mitochondrial lipid peroxidation, quantified using the innovative fluorescent ratiometric probe MitoCLox, takes place prior to the onset of ferroptotic cell death. The mitochondria-targeted antioxidant SkQ1 hinders mitochondrial lipid peroxidation and thwarts ferroptosis, all while leaving unaffected the buildup of reactive oxygen species within the cytoplasm, an antecedent to mitochondrial lipid peroxidation. Similarly, the redox agent methylene blue, impeding the genesis of reactive oxygen species in complex I of the electron transport chain, also imparts a comparable protective effect. These findings collectively imply that reactive oxygen species originating from complex I might hold particular significance in fomenting mitochondrial lipid peroxidation, a pivotal trigger of ferroptosis.
    Language English
    Publishing date 2023-09-13
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 2486483-3
    ISSN 1867-2469 ; 1867-2450
    ISSN (online) 1867-2469
    ISSN 1867-2450
    DOI 10.1007/s12551-023-01126-w
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  5. Article ; Online: Innate Immunity as an Executor of the Programmed Death of Individual Organisms for the Benefit of the Entire Population.

    Chernyak, Boris V / Lyamzaev, Konstantin G / Mulkidjanian, Armen Y

    International journal of molecular sciences

    2021  Volume 22, Issue 24

    Abstract: In humans, over-activation of innate immunity in response to viral or bacterial infections often causes severe illness and death. Furthermore, similar mechanisms related to innate immunity can cause pathogenesis and death in sepsis, massive trauma ( ... ...

    Abstract In humans, over-activation of innate immunity in response to viral or bacterial infections often causes severe illness and death. Furthermore, similar mechanisms related to innate immunity can cause pathogenesis and death in sepsis, massive trauma (including surgery and burns), ischemia/reperfusion, some toxic lesions, and viral infections including COVID-19. Based on the reviewed observations, we suggest that such severe outcomes may be manifestations of a controlled suicidal strategy protecting the entire population from the spread of pathogens and from dangerous pathologies rather than an aberrant hyperstimulation of defense responses. We argue that innate immunity may be involved in the implementation of an altruistic programmed death of an organism aimed at increasing the well-being of the whole community. We discuss possible ways to suppress this atavistic program by interfering with innate immunity and suggest that combating this program should be a major goal of future medicine.
    MeSH term(s) Altruism ; Animals ; Apoptosis/immunology ; COVID-19/immunology ; Cell Death/immunology ; Cytokine Release Syndrome/immunology ; Cytokine Release Syndrome/mortality ; Humans ; Immunity, Innate/immunology ; Inflammasomes/immunology ; Inflammation/immunology ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Signal Transduction/immunology
    Chemical Substances Inflammasomes
    Language English
    Publishing date 2021-12-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms222413480
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  6. Article ; Online: Mitochondrial Lipid Peroxidation Is Responsible for Ferroptosis.

    Lyamzaev, Konstantin G / Panteleeva, Alisa A / Simonyan, Ruben A / Avetisyan, Armine V / Chernyak, Boris V

    Cells

    2023  Volume 12, Issue 4

    Abstract: Ferroptosis induced by erastin (an inhibitor of cystine transport) and butionine sulfoximine (an inhibitor of glutathione biosynthesis) was prevented by the mitochondria-targeted antioxidants SkQ1 and MitoTEMPO. These effects correlate with the ... ...

    Abstract Ferroptosis induced by erastin (an inhibitor of cystine transport) and butionine sulfoximine (an inhibitor of glutathione biosynthesis) was prevented by the mitochondria-targeted antioxidants SkQ1 and MitoTEMPO. These effects correlate with the prevention of mitochondrial lipid peroxidation, which precedes cell death. Methylene blue, a redox agent that inhibits the production of reactive oxygen species (ROS) in complex I of the mitochondrial electron transport chain, also inhibits ferroptosis and mitochondrial lipid peroxidation. Activation of ROS production in complex I with rotenone in the presence of ferrous iron stimulates lipid peroxidation in isolated mitochondria, while ROS produced by complex III are ineffective. SkQ1 and methylene blue inhibit lipid peroxidation. We suggest that ROS formed in complex I promote mitochondrial lipid peroxidation and ferroptosis.
    MeSH term(s) Lipid Peroxidation ; Ferroptosis ; Reactive Oxygen Species/metabolism ; Methylene Blue/metabolism ; Mitochondria/metabolism
    Chemical Substances Reactive Oxygen Species ; Methylene Blue (T42P99266K)
    Language English
    Publishing date 2023-02-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12040611
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  7. Article ; Online: Methylation of Phenyl Rings in Ester-Stabilized Phosphorus Ylides Vastly Enhances Their Protonophoric Activity.

    Rokitskaya, Tatyana I / Kirsanov, Roman S / Khailova, Ljudmila S / Panteleeva, Alisa A / Lyamzaev, Konstantin G / Korshunova, Galina A / Kotova, Elena A / Antonenko, Yuri N

    Chembiochem : a European journal of chemical biology

    2024  Volume 25, Issue 7, Page(s) e202300848

    Abstract: We have recently discovered that ester-stabilized phosphorus ylides, resulting from deprotonation of a phosphonium salt such as [Ph3PCH2COOR], can transfer protons across artificial and biological membranes. To create more effective cationic ... ...

    Abstract We have recently discovered that ester-stabilized phosphorus ylides, resulting from deprotonation of a phosphonium salt such as [Ph3PCH2COOR], can transfer protons across artificial and biological membranes. To create more effective cationic protonophores, we synthesized similar phosphonium salts with one ((heptyloxycarbonylmethyl)(p-tolyl)bromide) or two ((butyloxycarbonylmethyl)(3,5-xylyl)osphonium bromide) methyl substituents in the phenyl groups. The methylation enormously augmented both protonophoric activity of the ylides on planar bilayer lipid membrane (BLM) and uncoupling of mammalian mitochondria, which correlated with strongly accelerated flip-flop of their cationic precursors across the BLM.
    MeSH term(s) Animals ; Mitochondria, Liver/metabolism ; Phosphorus/metabolism ; Esters/metabolism ; Bromides/metabolism ; Methylation ; Lipid Bilayers/metabolism ; Mammals
    Chemical Substances Phosphorus (27YLU75U4W) ; Esters ; Bromides ; Lipid Bilayers
    Language English
    Publishing date 2024-03-04
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2020469-3
    ISSN 1439-7633 ; 1439-4227
    ISSN (online) 1439-7633
    ISSN 1439-4227
    DOI 10.1002/cbic.202300848
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  8. Article ; Online: Synthesis of Triphenylphosphonium-Linked Derivative of 3,5-Di

    Kirsanov, Roman S / Khailova, Ljudmila S / Rokitskaya, Tatyana I / Lyamzaev, Konstantin G / Panteleeva, Alisa A / Nazarov, Pavel A / Firsov, Alexander M / Iaubasarova, Iliuza R / Korshunova, Galina A / Kotova, Elena A / Antonenko, Yuri N

    ACS omega

    2024  Volume 9, Issue 10, Page(s) 11551–11561

    Abstract: Mitochondrial uncouplers are actively sought as potential therapeutics. Here, we report the first successful synthesis of mitochondria-targeted derivatives of the highly potent uncoupler 3,5- ... ...

    Abstract Mitochondrial uncouplers are actively sought as potential therapeutics. Here, we report the first successful synthesis of mitochondria-targeted derivatives of the highly potent uncoupler 3,5-di
    Language English
    Publishing date 2024-02-29
    Publishing country United States
    Document type Journal Article
    ISSN 2470-1343
    ISSN (online) 2470-1343
    DOI 10.1021/acsomega.3c08621
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  9. Article ; Online: Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria

    Golenkina, Ekaterina A / Viryasova, Galina M / Galkina, Svetlana I / Kondratenko, Natalia D / Gaponova, Tatjana V / Romanova, Yulia M / Lyamzaev, Konstantin G / Chernyak, Boris V / Sud'ina, Galina F

    Frontiers in immunology

    2024  Volume 15, Page(s) 1295150

    Abstract: Neutrophils play a primary role in protecting our body from pathogens. When confronted with invading bacteria, neutrophils begin to produce leukotriene B4, a potent chemoattractant that, in cooperation with the primary bacterial chemoattractant fMLP, ... ...

    Abstract Neutrophils play a primary role in protecting our body from pathogens. When confronted with invading bacteria, neutrophils begin to produce leukotriene B4, a potent chemoattractant that, in cooperation with the primary bacterial chemoattractant fMLP, stimulates the formation of swarms of neutrophils surrounding pathogens. Here we describe a complex redox regulation that either stimulates or inhibits fMLP-induced leukotriene synthesis in an experimental model of neutrophils interacting with
    MeSH term(s) Neutrophils ; Leukotriene B4 ; Salmonella typhimurium ; Acetylcysteine/pharmacology ; Diamide/pharmacology ; Leukotrienes/pharmacology ; Chemotactic Factors ; Oxidation-Reduction ; Antioxidants/pharmacology ; Glutathione/pharmacology ; Sulfhydryl Compounds/pharmacology
    Chemical Substances Leukotriene B4 (1HGW4DR56D) ; Acetylcysteine (WYQ7N0BPYC) ; Diamide (10465-78-8) ; Leukotrienes ; Chemotactic Factors ; Antioxidants ; Glutathione (GAN16C9B8O) ; Sulfhydryl Compounds
    Language English
    Publishing date 2024-02-07
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1295150
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  10. Article ; Online: Relationship of Cytotoxic and Antimicrobial Effects of Triphenylphosphonium Conjugates with Various Quinone Derivatives.

    Nazarov, Pavel A / Zinovkina, Lyudmila A / Brezgunova, Anna A / Lyamzaev, Konstantin G / Golovin, Andrei V / Karakozova, Marina V / Kotova, Elena A / Plotnikov, Egor Yu / Zinovkin, Roman A / Skulachev, Maxim V / Antonenko, Yuri N

    Biochemistry. Biokhimiia

    2024  Volume 89, Issue 2, Page(s) 212–222

    Abstract: Quinone derivatives of triphenylphosphonium have proven themselves to be effective geroprotectors and antioxidants that prevent oxidation of cell components with participation of active free radicals - peroxide ( ... ...

    Abstract Quinone derivatives of triphenylphosphonium have proven themselves to be effective geroprotectors and antioxidants that prevent oxidation of cell components with participation of active free radicals - peroxide (RO
    MeSH term(s) Animals ; Mitochondria/metabolism ; Antioxidants/pharmacology ; Organophosphorus Compounds/pharmacology ; Plastoquinone/pharmacology ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/metabolism ; Antineoplastic Agents/pharmacology ; Mammals/metabolism ; Benzoquinones
    Chemical Substances triphenylphosphonium ; Antioxidants ; Organophosphorus Compounds ; quinone (3T006GV98U) ; Plastoquinone (OAC30J69CN) ; Anti-Bacterial Agents ; Antineoplastic Agents ; Benzoquinones
    Language English
    Publishing date 2024-03-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297924020032
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