Oxidative Modification of Redox Proteins: Role in the Regulation of HBL-100 Cell Proliferation

  • E. V. ShakhristovaEmail author
  • E. A. Stepovaya
  • E. V. Rudikov
  • V. V. Novitskii

HBL-100 breast epithelial cells were cultured with a blocker (N-ethylmaleimide) and protector (1,4-dithioerythritol) of SH groups. The study assessed changes in redox potential of glutathione and thioredoxin systems, intensity of oxidative modification of proteins, ROS production, and cell proliferation. The roles of thioredoxin system and protein oxidative modification in HBL-100 cell proliferation under redox status modulation were established. The role of carbonylated thioredoxin in arrest of the cell cycle in S-phase was demonstrated, which could be used for targeted therapy of the diseases accompanied by oxidative stress and disturbed redox status.

Key Words

redox regulation proliferation thioredoxin system oxidative protein modification carbonylated thioredoxin 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Arutyunyan AV, Dubinina EE, Zybina NN. Methods of Evaluation of Free-Radical Oxidation and Antioxidant Defense of the Organism. St. Petersburg, 2000. Russian.Google Scholar
  2. 2.
    Zenkov NK, Kozhin PM, Chechushkov AV, Menshchikova EB, Martinovich GG, Kandalintseva NV. Mazes of Nrf2 regulation. Biochemistry (Moscow). 2017;82(5):556-564.CrossRefGoogle Scholar
  3. 3.
    Men’shchikova EB, Zenkov NK, Lankin VZ, Bondar’ IA, Trufakin VA. Oxidative Stress: Pathological conditions and Diseases. Novosibirsk, 2008. Russian.Google Scholar
  4. 4.
    Shakhristova EV, Stepovaya EA, Rudikov EV, Novitskij VV. Patent RU No. 2651765. Method of determination of thioredoxin oxidative modification. Bull. No. 12. Published April 23, 2018.Google Scholar
  5. 5.
    Stepovaya EA, Shakhristova EV, Ryazantseva NV, Nosareva OL, Yakushina VD, Nosova AI, Gulaya VS, Stepanova EA, Chil’chigashev RI, Novitsky VV. The role of oxidative protein modification and the gluthatione system in modulation of the redox status of breast epithelial cells. Biomed. Khimiya. 2016;62(1):64-68. Russian.CrossRefGoogle Scholar
  6. 6.
    Brunelli L, Crow JP, Beckman JS. The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli. Arch. Biochem. Biophys. 1995;316(1):327-334.CrossRefGoogle Scholar
  7. 7.
    Butterfield DA, Dalle-Donne I. Redox proteomics: from protein modifications to cellular dysfunction and disease. Mass Spectrom. Rev. 2014;33(1):1-6.CrossRefGoogle Scholar
  8. 8.
    Halliwell B. Free radicals and antioxidants: updating a personal view. Nutr. Rev. 2012;70(5):257-265.CrossRefGoogle Scholar
  9. 9.
    Halliwell B, Whiteman M. Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br. J. Pharmacol. 2004;142(2):231-255.CrossRefGoogle Scholar
  10. 10.
    Harris IS, Treloar AE, Inoue S, Sasaki M, Gorrini C, Lee KC, Yung KY, Brenner D, Knobbe-Thomsen CB, Cox MA, Elia A, Berger T, Cescon DW, Adeoye A, Brüstle A, Molyneux SD, Mason JM, Li WY, Yamamoto K, Wakeham A, Berman HK, Khokha R, Done SJ, Kavanagh TJ, Lam CW, Mak TW. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell. 2015;27(2):211-222.CrossRefGoogle Scholar
  11. 11.
    Klaunig JE, Wang Z. Oxidative stress in carcinogenesis. Curr. Opin. Toxicol. 2018;7:116-121.CrossRefGoogle Scholar
  12. 12.
    Rahman I, Kode A, Biswas SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat. Protoc. 2006;1(6):3159-3165.CrossRefGoogle Scholar
  13. 13.
    Sahaf B, Heydari K, Herzenberg LA, Herzenberg LA. Lymphocyte surface thiol levels. Proc. Natl Acad. Sci. USA. 2003; 100(7):4001-4005.CrossRefGoogle Scholar
  14. 14.
    Tamura T, Stadtman TC. A new selenoprotein from human lung adenocarcinoma cells: purification, properties, and thioredoxin reductase activity. Proc. Natl Acad. Sci. USA. 1996;93(3):1006-1011.CrossRefGoogle Scholar
  15. 15.
    Wong CM, Bansal G, Marcocci L, Suzuki YJ. Proposed role of primary protein carbonylation in cell signaling. Redox Rep. 2012;17(2):90-94.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • E. V. Shakhristova
    • 1
    Email author
  • E. A. Stepovaya
    • 1
  • E. V. Rudikov
    • 1
  • V. V. Novitskii
    • 1
  1. 1.Siberian State Medical University, Ministry of Health of the Russian FederationTomskRussia

Personalised recommendations