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  1. Article ; Online: Binase treatment increases interferon sensitivity and apoptosis in SiHa cervical carcinoma cells by downregulating E6 and E7 human papilloma virus oncoproteins.

    Mitkevich, Vladimir A / Burnysheva, Ksenia M / Petrushanko, Irina Yu / Adzhubei, Alexei A / Schulga, Alexey A / Chumakov, Peter M / Makarov, Alexander A

    Oncotarget

    2017  Volume 8, Issue 42, Page(s) 72666–72675

    Abstract: In this study, we determined whether binase, a ribonuclease ... ...

    Abstract In this study, we determined whether binase, a ribonuclease from
    Language English
    Publishing date 2017-08-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.20199
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge.

    Mitkevich, Vladimir A / Burnysheva, Ksenia M / Ilinskaya, Olga N / Pace, C Nick / Makarov, Alexander A

    Oncoscience

    2014  Volume 1, Issue 11, Page(s) 738–744

    Abstract: The majority of known cytotoxic RNases are basic proteins which destroy intracellular RNA. Cationization of RNases is considered to be an effective strategy for strengthening their antitumor properties. We constructed a set of RNase Sa variants ... ...

    Abstract The majority of known cytotoxic RNases are basic proteins which destroy intracellular RNA. Cationization of RNases is considered to be an effective strategy for strengthening their antitumor properties. We constructed a set of RNase Sa variants consisting of charge reversal mutants, charge neutralization mutants, and variants with positively charged cluster at the N-terminus. All constructs retain a high level of catalytic activity and differ in net charge. Using acute myeloid leukemia cells Kasumi-1 we have shown that (i) cytotoxicity of RNase Sa mutants is linearly enhanced by cationization, (ii) the ability of cytotoxic mutants to induce cell death is caused by induction of apoptosis and (iii) localization of positive charge on N-terminus does not contribute to RNase Sa cytotoxicity. Capacity to induce apoptosis in malignant cells and the absence of necrotic effects make the RNase Sa mutants with high positive charge a suitable anti-cancer agent.
    Language English
    Publishing date 2014-11-10
    Publishing country United States
    Document type Journal Article
    ISSN 2331-4737
    ISSN 2331-4737
    DOI 10.18632/oncoscience.97
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Basal Glutathionylation of Na,K-ATPase α-Subunit Depends on Redox Status of Cells during the Enzyme Biosynthesis.

    Mitkevich, Vladimir A / Petrushanko, Irina Yu / Poluektov, Yuri M / Burnysheva, Ksenia M / Lakunina, Valentina A / Anashkina, Anastasia A / Makarov, Alexander A

    Oxidative medicine and cellular longevity

    2016  Volume 2016, Page(s) 9092328

    Abstract: Many viruses induce oxidative stress and cause S-glutathionylation of Cys residues of the host and viral proteins. Changes in cell functioning during viral infection may be associated with glutathionylation of a number of key proteins including Na,K- ... ...

    Abstract Many viruses induce oxidative stress and cause S-glutathionylation of Cys residues of the host and viral proteins. Changes in cell functioning during viral infection may be associated with glutathionylation of a number of key proteins including Na,K-ATPase which creates a gradient of sodium and potassium ions. It was found that Na,K-ATPase α-subunit has a basal glutathionylation which is not abrogated by reducing agent. We have shown that acute hypoxia leads to increase of total glutathionylation level of Na,K-ATPase α-subunit; however, basal glutathionylation of α-subunit increases under prolonged hypoxia only. The role of basal glutathionylation in Na,K-ATPase function remains unclear. Understanding significance of basal glutathionylation is complicated by the fact that there are no X-ray structures of Na,K-ATPase with the identified glutathione molecules. We have analyzed all X-ray structures of the Na,K-ATPase α-subunit from pig kidney and found that there are a number of isolated cavities with unresolved electron density close to the relevant cysteine residues. Analysis of the structures showed that this unresolved density in the structure can be occupied by glutathione associated with cysteine residues. Here, we discuss the role of basal glutathionylation of Na,K-ATPase α-subunit and provide evidence supporting the view that this modification is cotranslational.
    MeSH term(s) Animals ; Binding Sites ; Cell Hypoxia ; Cell Line ; Crystallography, X-Ray ; Cysteine/chemistry ; Cysteine/metabolism ; Glutathione/chemistry ; Glutathione/metabolism ; Immunoprecipitation ; Kidney/enzymology ; Kidney/metabolism ; Mice ; Molecular Dynamics Simulation ; Oxidation-Reduction ; Phosphines/pharmacology ; Protein Processing, Post-Translational/drug effects ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Protein Subunits/metabolism ; Sodium-Potassium-Exchanging ATPase/chemistry ; Sodium-Potassium-Exchanging ATPase/metabolism ; Swine
    Chemical Substances Phosphines ; Protein Subunits ; tris(2-carboxyethyl)phosphine (22OAC2MO2S) ; Sodium-Potassium-Exchanging ATPase (EC 3.6.3.9) ; Glutathione (GAN16C9B8O) ; Cysteine (K848JZ4886)
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article
    ISSN 1942-0994
    ISSN (online) 1942-0994
    DOI 10.1155/2016/9092328
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Direct interaction of beta-amyloid with Na,K-ATPase as a putative regulator of the enzyme function.

    Petrushanko, Irina Yu / Mitkevich, Vladimir A / Anashkina, Anastasia A / Adzhubei, Alexei A / Burnysheva, Ksenia M / Lakunina, Valentina A / Kamanina, Yulia V / Dergousova, Elena A / Lopina, Olga D / Ogunshola, Omolara O / Bogdanova, Anna Yu / Makarov, Alexander A

    Scientific reports

    2016  Volume 6, Page(s) 27738

    Abstract: By maintaining the Na(+) and K(+) transmembrane gradient mammalian Na,K-ATPase acts as a key regulator of neuronal electrotonic properties. Na,K-ATPase has an important role in synaptic transmission and memory formation. Accumulation of beta-amyloid (Aβ) ...

    Abstract By maintaining the Na(+) and K(+) transmembrane gradient mammalian Na,K-ATPase acts as a key regulator of neuronal electrotonic properties. Na,K-ATPase has an important role in synaptic transmission and memory formation. Accumulation of beta-amyloid (Aβ) at the early stages of Alzheimer's disease is accompanied by reduction of Na,K-ATPase functional activity. The molecular mechanism behind this phenomenon is not known. Here we show that the monomeric Aβ(1-42) forms a tight (Kd of 3 μM), enthalpy-driven equimolar complex with α1β1 Na,K-ATPase. The complex formation results in dose-dependent inhibition of the enzyme hydrolytic activity. The binding site of Aβ(1-42) is localized in the "gap" between the alpha- and beta-subunits of Na,K-ATPase, disrupting the enzyme functionality by preventing the subunits from shifting towards each other. Interaction of Na,K-ATPase with exogenous Aβ(1-42) leads to a pronounced decrease of the enzyme transport and hydrolytic activity and Src-kinase activation in neuroblastoma cells SH-SY5Y. This interaction allows regulation of Na,K-ATPase activity by short-term increase of the Aβ(1-42) level. However prolonged increase of Aβ(1-42) level under pathological conditions could lead to chronical inhibition of Na,K-ATPase and disruption of neuronal function. Taken together, our data suggest the role of beta-amyloid as a novel physiological regulator of Na,K-ATPase.
    Language English
    Publishing date 2016-06-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep27738
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  5. Article ; Online: Amyloid-β Increases Activity of Proteasomes Capped with 19S and 11S Regulators.

    Morozov, Alexey V / Kulikova, Alexandra A / Astakhova, Tatiana M / Mitkevich, Vladimir A / Burnysheva, Ksenia M / Adzhubei, Alexei A / Erokhov, Pavel A / Evgen'ev, Michail B / Sharova, Natalia P / Karpov, Vadim L / Makarov, Alexander A

    Journal of Alzheimer's disease : JAD

    2016  Volume 54, Issue 2, Page(s) 763–776

    Abstract: Accumulation of amyloid-β (Aβ) in neurons accompanies Alzheimer's disease progression. In the cytoplasm Aβ influences activity of proteasomes, the multisubunit protein complexes that hydrolyze the majority of intracellular proteins. However, the manner ... ...

    Abstract Accumulation of amyloid-β (Aβ) in neurons accompanies Alzheimer's disease progression. In the cytoplasm Aβ influences activity of proteasomes, the multisubunit protein complexes that hydrolyze the majority of intracellular proteins. However, the manner in which Aβ affects the proteolytic activity of proteasomes has not been established. In this study the effect of Aβ42 and Aβ42 with isomerized Asp7 on activity of different forms of proteasomes has been analyzed. It has been shown that Aβ peptides efficiently reduce activity of the 20S proteasomes, but increase activity of the 20S proteasomes capped with the 19S and/or 11S regulators. Modulation of proteasome activity is mainly determined by the C-terminal segment of Aβ (amino acids 17-42). This study demonstrated an important role of proteasome regulators in the interplay between Aβ and the proteasomes.
    Language English
    Publishing date 2016-09-06
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-160491
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6084: Show issues Location:
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  6. Article: Ribonuclease binase apoptotic signature in leukemic Kasumi-1 cells

    Mitkevich, Vladimir A / Kretova, Olga V / Petrushanko, Irina Yu / Burnysheva, Ksenia M / Sosin, Dmitry V / Simonenko, Olga V / Ilinskaya, Olga N / Tchurikov, Nickolai A / Makarov, Alexander A

    Biochimie. 2013 June, v. 95, no. 6

    2013  

    Abstract: Cytotoxic exogenous RNases triggering apoptotic response in malignant cells have potential as anticancer drugs; surprisingly, detailed characterization of the RNase-induced apoptosis has not been conducted so far. Here we show that a cytotoxic RNase from ...

    Abstract Cytotoxic exogenous RNases triggering apoptotic response in malignant cells have potential as anticancer drugs; surprisingly, detailed characterization of the RNase-induced apoptosis has not been conducted so far. Here we show that a cytotoxic RNase from Bacillus intermedius (binase) induces extrinsic and intrinsic apoptotic pathways in leukemic Kasumi-1 cells. The experiments were performed using TaqMan Array Human Apoptosis 96-well Plate for gene expression analysis, and flow cytometry. Cytometric studies demonstrated dissipation of the mitochondrial membrane potential, opening of mitochondrial permeability transition pores, activation of caspases, increase of intracellular Ca²⁺ and decrease of reactive oxygen species levels. We found that expression of 62 apoptotic genes is up-regulated, including 16 genes that are highly up-regulated, and only one gene was found to be down-regulated. The highest, 16 fold increase of the expression level was observed for TNF gene. Highly up-regulated genes also include the non-canonical NF-κB signaling pathway and inflammatory caspases 1,4. The obtained results suggest that binase induces evolutionary acquired cellular response to a microbial agent and triggers unusual apoptosis pathway.
    Keywords Bacillus intermedius ; antineoplastic agents ; apoptosis ; calcium ; caspases ; cytotoxicity ; flow cytometry ; gene expression ; gene expression regulation ; genes ; humans ; membrane potential ; mitochondrial membrane ; permeability ; reactive oxygen species ; ribonucleases ; signal transduction ; transcription factor NF-kappa B
    Language English
    Dates of publication 2013-06
    Size p. 1344-1349.
    Publishing place Elsevier Masson SAS
    Document type Article
    ZDB-ID 120345-9
    ISSN 0300-9084
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2013.02.016
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 72/375: Show issues

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  7. Article ; Online: Ribonuclease binase apoptotic signature in leukemic Kasumi-1 cells.

    Mitkevich, Vladimir A / Kretova, Olga V / Petrushanko, Irina Yu / Burnysheva, Ksenia M / Sosin, Dmitry V / Simonenko, Olga V / Ilinskaya, Olga N / Tchurikov, Nickolai A / Makarov, Alexander A

    Biochimie

    2013  Volume 95, Issue 6, Page(s) 1344–1349

    Abstract: Cytotoxic exogenous RNases triggering apoptotic response in malignant cells have potential as anticancer drugs; surprisingly, detailed characterization of the RNase-induced apoptosis has not been conducted so far. Here we show that a cytotoxic RNase from ...

    Abstract Cytotoxic exogenous RNases triggering apoptotic response in malignant cells have potential as anticancer drugs; surprisingly, detailed characterization of the RNase-induced apoptosis has not been conducted so far. Here we show that a cytotoxic RNase from Bacillus intermedius (binase) induces extrinsic and intrinsic apoptotic pathways in leukemic Kasumi-1 cells. The experiments were performed using TaqMan Array Human Apoptosis 96-well Plate for gene expression analysis, and flow cytometry. Cytometric studies demonstrated dissipation of the mitochondrial membrane potential, opening of mitochondrial permeability transition pores, activation of caspases, increase of intracellular Ca(2+) and decrease of reactive oxygen species levels. We found that expression of 62 apoptotic genes is up-regulated, including 16 genes that are highly up-regulated, and only one gene was found to be down-regulated. The highest, 16 fold increase of the expression level was observed for TNF gene. Highly up-regulated genes also include the non-canonical NF-κB signaling pathway and inflammatory caspases 1,4. The obtained results suggest that binase induces evolutionary acquired cellular response to a microbial agent and triggers unusual apoptosis pathway.
    MeSH term(s) Apoptosis/drug effects ; Cell Line, Tumor ; Endoribonucleases/metabolism ; Endoribonucleases/pharmacology ; Flow Cytometry ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Mitochondrial Membrane Transport Proteins/drug effects ; Mitochondrial Membrane Transport Proteins/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcriptome/drug effects
    Chemical Substances Mitochondrial Membrane Transport Proteins ; mitochondrial permeability transition pore ; Endoribonucleases (EC 3.1.-) ; ribonuclease T(2) (EC 3.1.27.1)
    Language English
    Publishing date 2013-06
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120345-9
    ISSN 1638-6183 ; 0300-9084
    ISSN (online) 1638-6183
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2013.02.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.135: Show issues Location:
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