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  1. Article: Effect of β-amyloid on blood-brain barrier properties and function.

    Petrushanko, Irina Yu / Mitkevich, Vladimir A / Makarov, Alexander A

    Biophysical reviews

    2023  Volume 15, Issue 2, Page(s) 183–197

    Abstract: The deposition of beta-amyloid (Aβ) aggregates in the brain, accompanied by impaired cognitive function, is a characteristic feature of Alzheimer's disease (AD). An important role in this process is played by vascular disorders, in particular, a ... ...

    Abstract The deposition of beta-amyloid (Aβ) aggregates in the brain, accompanied by impaired cognitive function, is a characteristic feature of Alzheimer's disease (AD). An important role in this process is played by vascular disorders, in particular, a disturbance of the blood-brain barrier (BBB). The BBB controls the entry of Aβ from plasma to the brain via the receptor for advanced glycation end products (RAGE) and the removal of brain-derived Aβ via the low-density lipoprotein receptor-related protein (LRP1). The balance between the input of Aβ to the brain from the periphery and its output is disturbed during AD. Aβ changes the redox-status of BBB cells, which in turn changes the functioning of mitochondria and disrupts the barrier function of endothelial cells by affecting tight junction proteins. Aβ oligomers have the greatest toxic effect on BBB cells, and oligomers are most rapidly transferred by transcytosis from the brain side of the BBB to the blood side. Both the cytotoxic effect of Aβ and the impairment of barrier function are partly due to the interaction of Aβ monomers and oligomers with membrane-bound RAGE. AD therapies based on the disruption of this interaction or the creation of decoys for Aβ are being developed. The question of the transfer of various Aβ isoforms through the BBB is important, since it can influence the development of AD. It is shown that the rate of input of Aβ
    Language English
    Publishing date 2023-04-05
    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/s12551-023-01052-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Post-translational modifications of beta-amyloid alter its transport in the blood-brain barrier

    Varshavskaya, Kseniya B / Petrushanko, Irina Yu / Mitkevich, Vladimir A / Barykin, Evgeny P / Makarov, Alexander A

    Frontiers in molecular neuroscience

    2024  Volume 17, Page(s) 1362581

    Abstract: One of the hallmarks of Alzheimer's disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational ... ...

    Abstract One of the hallmarks of Alzheimer's disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood-brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ
    Language English
    Publishing date 2024-03-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2024.1362581
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Glutathione Non-Covalent Binding Sites on Hemoglobin and Major Glutathionylation Target betaCys93 Are Conservative among Both Hypoxia-Sensitive and Hypoxia-Tolerant Mammal Species.

    Anashkina, Anastasia A / Simonenko, Sergey Yu / Orlov, Yuriy L / Petrushanko, Irina Yu

    International journal of molecular sciences

    2023  Volume 25, Issue 1

    Abstract: Intracellular tripeptide glutathione is an important agent of cell survival under hypoxia. Glutathione covalently binds to SH groups of hemoglobin cysteine residues, protecting them from irreversible oxidation, and changes its affinity to oxygen. Reduced ...

    Abstract Intracellular tripeptide glutathione is an important agent of cell survival under hypoxia. Glutathione covalently binds to SH groups of hemoglobin cysteine residues, protecting them from irreversible oxidation, and changes its affinity to oxygen. Reduced glutathione (GSH) can also form a noncovalent complex with hemoglobin. Previously, we showed that hemoglobin tetramer has four noncovalent binding sites of glutathione GSH molecules inside, two of which are released during hemoglobin transition to deoxy form. In this study, we characterized the conserved cysteine residues and residues of noncovalent glutathione binding sites in the sequences of a number of hypoxia-tolerant and hypoxia-sensitive mammals. The solvent accessibility of all HbA and HbB residues in oxy and deoxy forms was analyzed. The alpha subunit of all species considered was shown to have no conserved cysteines, whereas the beta subunit contains Cys93 residue, which is conserved across species and whose glutathionylation changes the affinity of hemoglobin for oxygen 5-6-fold. It was found that the key residues of noncovalent glutathione binding sites in both alpha and beta subunits are absolutely conserved in all species considered, suggesting a common mechanism of hemoglobin redox regulation for both hypoxia-sensitive and hypoxia-tolerant mammals.
    MeSH term(s) Animals ; Cysteine ; Hypoxia ; Oxygen ; Binding Sites ; Glutathione ; Hemoglobins ; Mammals
    Chemical Substances Cysteine (K848JZ4886) ; Oxygen (S88TT14065) ; Glutathione (GAN16C9B8O) ; Hemoglobins
    Language English
    Publishing date 2023-12-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25010053
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Docking and Molecular Dynamics-Based Identification of Interaction between Various Beta-Amyloid Isoforms and RAGE Receptor.

    Tolstova, Anna P / Adzhubei, Alexei A / Mitkevich, Vladimir A / Petrushanko, Irina Yu / Makarov, Alexander A

    International journal of molecular sciences

    2022  Volume 23, Issue 19

    Abstract: Beta-amyloid peptide (Aβ) is a ligand associated with RAGE (Advanced glycosylation end product-specific receptor). Aβ is translocated in complexes with RAGE from the blood to brain across the blood-brain barrier (BBB) by transcytosis. Aβ and its isoforms ...

    Abstract Beta-amyloid peptide (Aβ) is a ligand associated with RAGE (Advanced glycosylation end product-specific receptor). Aβ is translocated in complexes with RAGE from the blood to brain across the blood-brain barrier (BBB) by transcytosis. Aβ and its isoforms are important factors in the Alzheimer's disease (AD) pathogenesis. However, interaction with RAGE was previously studied for Aβ but not for its isoforms. The present study has been directed at identifying the key interaction interfaces between RAGE and Aβ isoforms (Aβ
    MeSH term(s) Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Blood-Brain Barrier/metabolism ; Humans ; Ligands ; Molecular Dynamics Simulation ; Peptide Fragments/metabolism ; Protein Isoforms/metabolism ; Receptor for Advanced Glycation End Products/metabolism
    Chemical Substances Amyloid beta-Peptides ; Ligands ; Peptide Fragments ; Protein Isoforms ; Receptor for Advanced Glycation End Products
    Language English
    Publishing date 2022-10-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms231911816
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: RNases Disrupt the Adaptive Potential of Malignant Cells: Perspectives for Therapy.

    Mitkevich, Vladimir Alexandrovich / Petrushanko, Irina Yu / Makarov, Alexander Alexander

    Frontiers in pharmacology

    2019  Volume 10, Page(s) 922

    Abstract: Exogenous RNases are selectively toxic to tumor cells. The reasons for this selectivity are not quite clear and should be searched for in the properties that distinguish malignant from normal cells. During onco-transformation, cells acquire properties ... ...

    Abstract Exogenous RNases are selectively toxic to tumor cells. The reasons for this selectivity are not quite clear and should be searched for in the properties that distinguish malignant from normal cells. During onco-transformation, cells acquire properties allowing them to adapt to the altered microenvironment, such as resistance to hypoxia, changes in intracellular pH, disruption of ion transport, reduced adhesion and increased mobility, and production of specific exosomes. These adaptation mechanisms distinguish malignant cells from normal ones and give them a competitive advantage, ensuring survival and spread in the organism. Here, we analyze if the directed cytotoxic effect of exogenous RNases is linked to the disruption of the adaptive potential of tumor cells and how it can be used in anticancer therapy.
    Language English
    Publishing date 2019-08-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2019.00922
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Entropy Analysis of Protein Sequences Reveals a Hierarchical Organization.

    Anashkina, Anastasia A / Petrushanko, Irina Yu / Ziganshin, Rustam H / Orlov, Yuriy L / Nekrasov, Alexei N

    Entropy (Basel, Switzerland)

    2021  Volume 23, Issue 12

    Abstract: Background: Analyzing the local sequence content in proteins, earlier we found that amino acid residue frequencies differ on various distances between amino acid positions in the sequence, assuming the existence of structural units.: Methods: We used ...

    Abstract Background: Analyzing the local sequence content in proteins, earlier we found that amino acid residue frequencies differ on various distances between amino acid positions in the sequence, assuming the existence of structural units.
    Methods: We used informational entropy of protein sequences to find that the structural unit of proteins is a block of adjacent amino acid residues-"information unit". The ANIS (ANalysis of Informational Structure) method uses these information units for revealing hierarchically organized Elements of the Information Structure (ELIS) in amino acid sequences.
    Results: The developed mathematical apparatus gives stable results on the structural unit description even with a significant variation in the parameters. The optimal length of the information unit is five, and the number of allowed substitutions is one. Examples of the application of the method for the design of protein molecules, intermolecular interactions analysis, and the study of the mechanisms of functioning of protein molecular machines are given.
    Conclusions: ANIS method makes it possible not only to analyze native proteins but also to design artificial polypeptide chains with a given spatial organization and, possibly, function.
    Language English
    Publishing date 2021-12-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2014734-X
    ISSN 1099-4300 ; 1099-4300
    ISSN (online) 1099-4300
    ISSN 1099-4300
    DOI 10.3390/e23121647
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Interaction Interface of Aβ

    Adzhubei, Alexei A / Tolstova, Anna P / Strelkova, Maria A / Mitkevich, Vladimir A / Petrushanko, Irina Yu / Makarov, Alexander A

    Biomedicines

    2022  Volume 10, Issue 7

    Abstract: Alzheimer's disease (AD) is a neurodegenerative disease accompanied by progressive cognitive and memory dysfunction due to disruption of normal electrotonic properties of neurons and neuronal loss. The Na,K-ATPase interaction with beta amyloid (Aβ) plays ...

    Abstract Alzheimer's disease (AD) is a neurodegenerative disease accompanied by progressive cognitive and memory dysfunction due to disruption of normal electrotonic properties of neurons and neuronal loss. The Na,K-ATPase interaction with beta amyloid (Aβ) plays an important role in AD pathogenesis. It has been shown that Na,K-ATPase activity in the AD brain was significantly lower than those in age-matched control brain. The interaction of Aβ
    Language English
    Publishing date 2022-07-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10071663
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  8. Article ; Online: The Inactivation of LPS Biosynthesis Genes in

    Seregina, Tatiana A / Petrushanko, Irina Yu / Shakulov, Rustem S / Zaripov, Pavel I / Makarov, Alexander A / Mitkevich, Vladimir A / Mironov, Alexander S

    Cells

    2022  Volume 11, Issue 17

    Abstract: Impaired lipopolysaccharide biosynthesis in Gram-negative bacteria results in the "deep rough" phenotype, which is characterized by increased sensitivity of cells to various hydrophobic compounds, including antibiotics novobiocin, actinomycin D, ... ...

    Abstract Impaired lipopolysaccharide biosynthesis in Gram-negative bacteria results in the "deep rough" phenotype, which is characterized by increased sensitivity of cells to various hydrophobic compounds, including antibiotics novobiocin, actinomycin D, erythromycin, etc. The present study showed that
    MeSH term(s) Adenosine Diphosphate/metabolism ; Anti-Bacterial Agents/pharmacology ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/chemistry ; Heptoses/chemistry ; Heptoses/metabolism ; Lipopolysaccharides/chemistry ; Lipopolysaccharides/pharmacology ; NADP/metabolism ; Oxidative Stress
    Chemical Substances Anti-Bacterial Agents ; Escherichia coli Proteins ; Heptoses ; Lipopolysaccharides ; NADP (53-59-8) ; Adenosine Diphosphate (61D2G4IYVH)
    Language English
    Publishing date 2022-08-27
    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/cells11172667
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Expression level of CD117 (KIT) on ovarian cancer extracellular vesicles correlates with tumor aggressiveness.

    Shnaider, Polina V / Petrushanko, Irina Yu / Aleshikova, Olga I / Babaeva, Nataliya A / Ashrafyan, Lev A / Borovkova, Ekaterina I / Dobrokhotova, Julia E / Borovkov, Ivan M / Shender, Victoria O / Khomyakova, Elena

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1057484

    Abstract: Ovarian cancer is known to be the most lethal malignancy among all gynecological cancers affecting a large number of women worldwide. The treatment of ovarian cancer is challenging due to the high recurrence rate of the disease and is further complicated ...

    Abstract Ovarian cancer is known to be the most lethal malignancy among all gynecological cancers affecting a large number of women worldwide. The treatment of ovarian cancer is challenging due to the high recurrence rate of the disease and is further complicated by acquired chemoresistance. Most ovarian cancer deaths are the result of the metastatic spread of drug-resistant cells. The theory of cancer stem cells (CSC) suggests that both tumor initiation and progression are driven by a population of undifferentiated capable of self-renewal, tumor initiation and development of chemoresistance. The CD117 mast/stem cell growth factor receptor (KIT) is the most commonly used marker for ovarian CSCs. Here, we analyze the correlation between CD117 expression and histological tumor type in ovarian cancer cell lines (SK-OV-3 and MES-OV) and in small/medium extracellular vesicles (EVs) isolated from the urine of ovarian cancer patients. We have demonstrated that the abundance of CD117 on cells and EVs is correlated with tumor grade and therapy resistance status. Moreover, using small EVs isolated from ovarian cancer ascites, it was shown that recurrent disease is characterized by a much higher abundance of CD117 on EVs than primary tumor.
    Language English
    Publishing date 2023-02-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1057484
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Changes in Hemoglobin Properties in Complex with Glutathione and after Glutathionylation.

    Kuleshova, Iuliia D / Zaripov, Pavel I / Poluektov, Yuri M / Anashkina, Anastasia A / Kaluzhny, Dmitry N / Parshina, Evgeniia Yu / Maksimov, Georgy V / Mitkevich, Vladimir A / Makarov, Alexander A / Petrushanko, Irina Yu

    International journal of molecular sciences

    2023  Volume 24, Issue 17

    Abstract: Hemoglobin is the main protein of red blood cells that provides oxygen transport to all cells of the human body. The ability of hemoglobin to bind the main low-molecular-weight thiol of the cell glutathione, both covalently and noncovalently, is not only ...

    Abstract Hemoglobin is the main protein of red blood cells that provides oxygen transport to all cells of the human body. The ability of hemoglobin to bind the main low-molecular-weight thiol of the cell glutathione, both covalently and noncovalently, is not only an important part of the antioxidant protection of red blood cells, but also affects its affinity for oxygen in both cases. In this study, the properties of oxyhemoglobin in complex with reduced glutathione (GSH) and properties of glutathionylated hemoglobin bound to glutathione via an SS bond were characterized. For this purpose, the methods of circular dichroism, Raman spectroscopy, infrared spectroscopy, tryptophan fluorescence, differential scanning fluorimetry, and molecular modeling were used. It was found that the glutathionylation of oxyhemoglobin caused changes in the secondary structure of the protein, reducing the alpha helicity, but did not affect the heme environment, tryptophan fluorescence, and the thermostability of the protein. In the noncovalent complex of oxyhemoglobin with reduced glutathione, the secondary structure of hemoglobin remained almost unchanged; however, changes in the heme environment and the microenvironment of tryptophans, as well as a decrease in the protein's thermal stability, were observed. Thus, the formation of a noncovalent complex of hemoglobin with glutathione makes a more significant effect on the tertiary and quaternary structure of hemoglobin than glutathionylation, which mainly affects the secondary structure of the protein. The obtained data are important for understanding the functioning of glutathionylated hemoglobin, which is a marker of oxidative stress, and hemoglobin in complex with GSH, which appears to deposit GSH and release it during deoxygenation to increase the antioxidant protection of cells.
    MeSH term(s) Humans ; Oxyhemoglobins ; Antioxidants ; Tryptophan ; Hemoglobins ; Glutathione ; Heme ; Oxygen
    Chemical Substances Oxyhemoglobins ; Antioxidants ; Tryptophan (8DUH1N11BX) ; Hemoglobins ; Glutathione (GAN16C9B8O) ; Heme (42VZT0U6YR) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2023-08-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241713557
    Database MEDical Literature Analysis and Retrieval System OnLINE

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