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  1. Article ; Online: A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse.

    Varlamova, Elena G / Uspalenko, Nina I / Khmil, Natalia V / Shigaeva, Maria I / Stepanov, Mikhail R / Ananyan, Mikhail A / Timchenko, Maria A / Molchanov, Maxim V / Mironova, Galina D / Turovsky, Egor A

    International journal of molecular sciences

    2023  Volume 24, Issue 14

    Abstract: Cerebral ischemia, and, as a result, insult, attacks up to 15 million people yearly in the world. In this connection, the development of effective preventive programs and methods of therapy has become one of the most urgent problems in modern angiology ... ...

    Abstract Cerebral ischemia, and, as a result, insult, attacks up to 15 million people yearly in the world. In this connection, the development of effective preventive programs and methods of therapy has become one of the most urgent problems in modern angiology and pharmacology. The cytoprotective action of taxifolin (TAX) in ischemia is well known, but its limitations are also known due to its poor solubility and low capacity to pass through the hematoencephalic barrier. Molecular mechanisms underlying the protective effect of TAX in complex systems such as the brain remain poorly understood. It is known that the main cell types of the brain are neurons, astrocytes, and microglia, which regulate the activity of each other through neuroglial interactions. In this work, a comparative study of cytoprotective mechanisms of the effect of TAX and its new water-soluble form aqua taxifolin (aqTAX) was performed on cultured brain cells under ischemia-like conditions (oxygen-glucose deprivation (OGD)) followed by the reoxygenation of the culture medium. The concentration dependences of the protective effects of both taxifolin forms were determined using fluorescence microscopy, PCR analysis, and vitality tests. It was found that TAX began to effectively inhibit necrosis and the late stages of apoptosis in the concentration range of 30-100 µg/mL, with aqTAX in the range of 10-30 µg/mL. At the level of gene expression, aqTAX affected a larger number of genes than TAX; enhanced the basic and OGD/R-induced expression of genes encoding ROS-scavenging proteins with a higher efficiency, as well as anti-inflammatory and antiapoptotic proteins; and lowered the level of excitatory glutamate receptors. As a result, aqTAX significantly inhibited the OGD-induced increase in the Ca
    MeSH term(s) Mice ; Animals ; Signal Transduction ; Quercetin/pharmacology ; Quercetin/metabolism ; Neurons/metabolism ; Brain Ischemia/drug therapy ; Brain Ischemia/metabolism ; Oxygen/metabolism ; Glucose/metabolism ; Cells, Cultured ; Ischemia/metabolism ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/metabolism ; Cell Survival
    Chemical Substances taxifolin (9SOB9E3987) ; Quercetin (9IKM0I5T1E) ; Oxygen (S88TT14065) ; Glucose (IY9XDZ35W2) ; Neuroprotective Agents
    Language English
    Publishing date 2023-07-14
    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/ijms241411436
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations.

    Bobylev, Alexander G / Yakupova, Elmira I / Bobyleva, Liya G / Molochkov, Nikolay V / Timchenko, Alexander A / Timchenko, Maria A / Kihara, Hiroshi / Nikulin, Alexey D / Gabdulkhakov, Azat G / Melnik, Tatiana N / Penkov, Nikita V / Lobanov, Michail Y / Kazakov, Alexey S / Kellermayer, Miklós / Mártonfalvi, Zsolt / Galzitskaya, Oxana V / Vikhlyantsev, Ivan M

    International journal of molecular sciences

    2023  Volume 24, Issue 2

    Abstract: A giant multidomain protein of striated and smooth vertebrate muscles, titin, consists of tandems of immunoglobulin (Ig)- and fibronectin type III (FnIII)-like domains representing β-sandwiches, as well as of disordered segments. Chicken smooth muscles ... ...

    Abstract A giant multidomain protein of striated and smooth vertebrate muscles, titin, consists of tandems of immunoglobulin (Ig)- and fibronectin type III (FnIII)-like domains representing β-sandwiches, as well as of disordered segments. Chicken smooth muscles express several titin isoforms of ~500-1500 kDa. Using various structural-analysis methods, we investigated in vitro nonspecific amyloid aggregation of the high-molecular-weight isoform of chicken smooth-muscle titin (SMT
    MeSH term(s) Animals ; Amyloid/metabolism ; Amyloidogenic Proteins/metabolism ; Chickens/metabolism ; Connectin/metabolism ; Muscle, Smooth/metabolism ; Avian Proteins/metabolism
    Chemical Substances Amyloid ; Amyloidogenic Proteins ; Connectin ; Avian Proteins
    Language English
    Publishing date 2023-01-05
    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/ijms24021056
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  3. Article ; Online: Myosin Binding Protein-C Forms Amyloid-Like Aggregates In Vitro.

    Bobyleva, Liya G / Shumeyko, Sergey A / Yakupova, Elmira I / Surin, Alexey K / Galzitskaya, Oxana V / Kihara, Hiroshi / Timchenko, Alexander A / Timchenko, Maria A / Penkov, Nikita V / Nikulin, Alexey D / Suvorina, Mariya Yu / Molochkov, Nikolay V / Lobanov, Mikhail Yu / Fadeev, Roman S / Vikhlyantsev, Ivan M / Bobylev, Alexander G

    International journal of molecular sciences

    2021  Volume 22, Issue 2

    Abstract: This work investigated in vitro aggregation and amyloid properties of skeletal myosin binding protein-C (sMyBP-C) interacting in vivo with proteins of thick and thin filaments in the sarcomeric A-disc. Dynamic light scattering (DLS) and transmission ... ...

    Abstract This work investigated in vitro aggregation and amyloid properties of skeletal myosin binding protein-C (sMyBP-C) interacting in vivo with proteins of thick and thin filaments in the sarcomeric A-disc. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) found a rapid (5-10 min) formation of large (>2 μm) aggregates. sMyBP-C oligomers formed both at the initial 5-10 min and after 16 h of aggregation. Small angle X-ray scattering (SAXS) and DLS revealed sMyBP-C oligomers to consist of 7-10 monomers. TEM and atomic force microscopy (AFM) showed sMyBP-C to form amorphous aggregates (and, to a lesser degree, fibrillar structures) exhibiting no toxicity on cell culture. X-ray diffraction of sMyBP-C aggregates registered reflections attributed to a cross-β quaternary structure. Circular dichroism (CD) showed the formation of the amyloid-like structure to occur without changes in the sMyBP-C secondary structure. The obtained results indicating a high in vitro aggregability of sMyBP-C are, apparently, a consequence of structural features of the domain organization of proteins of this family. Formation of pathological amyloid or amyloid-like sMyBP-C aggregates in vivo is little probable due to amino-acid sequence low identity (<26%), alternating ordered/disordered regions in the protein molecule, and S-S bonds providing for general stability.
    MeSH term(s) Amino Acid Sequence ; Amyloid/chemistry ; Amyloid/metabolism ; Amyloid/ultrastructure ; Carrier Proteins/chemistry ; Carrier Proteins/metabolism ; Chromatography, High Pressure Liquid ; Circular Dichroism ; Dynamic Light Scattering ; In Vitro Techniques ; Kinetics ; Mass Spectrometry ; Models, Molecular ; Protein Aggregates ; Protein Aggregation, Pathological ; Protein Conformation ; Structure-Activity Relationship ; X-Ray Diffraction
    Chemical Substances Amyloid ; Carrier Proteins ; Protein Aggregates ; myosin-binding protein C
    Language English
    Publishing date 2021-01-13
    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/ijms22020731
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Analyzing and mapping sweat metabolomics by high-resolution NMR spectroscopy.

    Kutyshenko, Viktor P / Molchanov, Maxim / Beskaravayny, Peter / Uversky, Vladimir N / Timchenko, Maria A

    PloS one

    2011  Volume 6, Issue 12, Page(s) e28824

    Abstract: The content of human sweat is studied by high-resolution NMR, and the majority of organic components most often found in sweat of conditionally healthy people are identified. Original and simple tools are designed for sweat sampling from different areas ... ...

    Abstract The content of human sweat is studied by high-resolution NMR, and the majority of organic components most often found in sweat of conditionally healthy people are identified. Original and simple tools are designed for sweat sampling from different areas of human body. The minimal surface area needed for sampling is in the range of 50-100 cm(2). On all the surface parts of the human body examined in this work, the main constituents forming a sweat metabolic profile are lactate, glycerol, pyruvate, and serine. The only exception is the sole of the foot (planta pedis), where trace amounts of glycerol are found. An attempt is made to explain the presence of specified metabolites and their possible origin.
    MeSH term(s) Adult ; Child ; Child, Preschool ; Female ; Humans ; Magnetic Resonance Spectroscopy/methods ; Male ; Metabolomics ; Middle Aged ; Sweat/metabolism
    Language English
    Publishing date 2011-12-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0028824
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  5. Article ; Online: Different amyloid aggregation of smooth muscles titin in vitro.

    Yakupova, Elmira I / Vikhlyantsev, Ivan M / Bobyleva, Liya G / Penkov, Nikita V / Timchenko, Alexander A / Timchenko, Maria A / Enin, Gennady A / Khutzian, Sergei S / Selivanova, Olga M / Bobylev, Alexander G

    Journal of biomolecular structure & dynamics

    2017  Volume 36, Issue 9, Page(s) 2237–2248

    Abstract: A comparative study of amyloid properties of the aggregates of smooth muscle titin (SMT) from chicken gizzard was carried out. These aggregates were formed in two solutions: 0.15 M glycine-KOH, pH 7.2-7.4 (SMT(Gly)) and 0.2 M KCl, 10 mM imidazole, pH 7.0 ...

    Abstract A comparative study of amyloid properties of the aggregates of smooth muscle titin (SMT) from chicken gizzard was carried out. These aggregates were formed in two solutions: 0.15 M glycine-KOH, pH 7.2-7.4 (SMT(Gly)) and 0.2 M KCl, 10 mM imidazole, pH 7.0 (SMT(KCl)). Electron microscopy data showed that SMT aggregates has an amorphous structure in both cases. The results of atomic-force microscopy demonstrated slight differences in morphology in two types of aggregates. The SMT(Gly) aggregates were represented as branching chains, composed of spherical aggregates approximately 300-500 nm in diameter and up to 35 nm in height. The SMT(KCl) aggregates formed sponge-like structures with strands of 8-10 nm in height. Structural analysis of SMT aggregates by X-ray diffraction revealed the presence of cross-β-sheet structure in the samples under study. In the presence of SMT(Gly) aggregates, thioflavine T fluorescence intensity was higher (~3-fold times) compared with that in the presence of SMT(KCl) aggregates. Congo red-stained SMT(Gly) aggregates had yellow to apple-green birefringence under polarized light, which was not observed for SMT(KCl) aggregates. Dynamic light scattering data showed the similar rate of aggregation for both types of aggregates, though SMT(KCl) aggregates were able to partially disaggregate under increased ionic strength of the solution. The ability of SMT to aggregation followed by disaggregation may be functionally significant in the cell.
    MeSH term(s) Amyloid/chemistry ; Amyloid/metabolism ; Amyloid/ultrastructure ; Benzothiazoles/chemistry ; Connectin/chemistry ; Connectin/isolation & purification ; Connectin/metabolism ; Dynamic Light Scattering ; Microscopy, Atomic Force ; Muscle, Smooth/metabolism ; Protein Aggregates ; Protein Aggregation, Pathological ; Spectrophotometry ; X-Ray Diffraction
    Chemical Substances Amyloid ; Benzothiazoles ; Connectin ; Protein Aggregates ; thioflavin T (2390-54-7)
    Language English
    Publishing date 2017-07-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2017.1348988
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  6. Article: Solution structure and dynamics of the chimeric SH3 domains, SHH- and SHA-"Bergeracs".

    Kutyshenko, Victor P / Prokhorov, Dmitry A / Timchenko, Maria A / Kudrevatykh, Yuri A / Gushchina, Liubov' V / Khristoforov, Vladimir S / Filimonov, Vladimir V / Uversky, Vladimir N

    Biochimica et biophysica acta

    2009  Volume 1794, Issue 12, Page(s) 1813–1822

    Abstract: Two chimeric proteins, SHcapital EN, Cyrillic and SHA of the "SH3-Bergerac" family (where the beta-turn N47D48 in spectrin SH3 domain was substituted for KITVNGKTYE or KATANGKTYE sequences, respectively), were analyzed by high-resolution NMR to resolve ... ...

    Abstract Two chimeric proteins, SHcapital EN, Cyrillic and SHA of the "SH3-Bergerac" family (where the beta-turn N47D48 in spectrin SH3 domain was substituted for KITVNGKTYE or KATANGKTYE sequences, respectively), were analyzed by high-resolution NMR to resolve their spatial structures and to analyze their dynamics. Although the presence of a stable beta-hairpin in the region of the insertion was confirmed, the introduced extension of the polypeptide chain in SHcapital EN, Cyrillic (approximately 17%) practically did not affect the total molecule topology. Interestingly, the introduced beta-hairpin had higher mobility in comparison with other protein regions. Finally, we performed a disorder prediction with the PONDR VSL2 algorithm and discovered that the inserted beta-hairpin in both SHH and SHA proteins exhibited significant propensity for intrinsic disorder and therefore for high mobility. In agreement with the experimental data, the predisposition for the increased intramolecular mobility was noticeably higher in SHA.
    MeSH term(s) Amino Acid Sequence ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Protein Folding ; Protein Structure, Secondary ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/genetics ; Solutions ; Thermodynamics ; src Homology Domains/genetics
    Chemical Substances Recombinant Fusion Proteins ; Solutions
    Language English
    Publishing date 2009-12
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbapap.2009.08.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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