The effect of hypochlorite-induced fibrinogen oxidation on the protein structure, fibrin self-assembly and fibrinolysis

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The article is dedicated to the structural-functional damage of fibrinogen treated with HOCl in the concentration range (10–100 µM). The MS/MS method detected 15 modified amino acid residues with a dose-dependent susceptibility to the oxidizing agent. Using turbidity measurements and confocal laser scanning microscopy, it has been shown that fibrinogen oxidation by 25–100 µM HOCl leads to the denser fibrin gel formation, as well as delayed polymerization onset and a decrease in the slope of the polymerization curve, presumably due to conformational changes of the protein. At lower HOCl concentration (10 µM), at least six amino acid residues were substantially modified (9–29%), but functionally such modified protein was not distinguishable from the native one. The detected amino acid residues are assumed to be ROS scavengers that prevent fibrinogen functions alteration.

Full Text

Restricted Access

About the authors

L. V. Yurina

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Author for correspondence.
Email: lyu.yurina@gmail.com
Russian Federation, Moscow

A. D. Vasilyeva

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Email: lyu.yurina@gmail.com
Russian Federation, Moscow

E. G. Evtushenko

Lomonosov Moscow State University

Email: lyu.yurina@gmail.com

Faculty of Chemistry

Russian Federation, Moscow

E. S. Gavrilina

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Email: lyu.yurina@gmail.com
Russian Federation, Moscow

S. I. Obydennyi

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation; Centre for Theoretical Problems of Physicochemical Pharmacology

Email: lyu.yurina@gmail.com
Russian Federation, Moscow; Moscow

I. A. Chabin

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation; Sechenov First Moscow State Medical University (Sechenov University)

Email: lyu.yurina@gmail.com
Russian Federation, Moscow; Moscow

M. I. Indeykina

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Email: lyu.yurina@gmail.com
Russian Federation, Moscow

A. S. Kononikhin

Talrose Institute for Energy Problems of Chemical Physics, N.N. Semenov Federal Center of Chemical Physics, Russian Academy of Sciences; Skolkovo Institute of Science and Technology

Email: lyu.yurina@gmail.com
Russian Federation, Moscow; Moscow

E. N. Nikolaev

Talrose Institute for Energy Problems of Chemical Physics, N.N. Semenov Federal Center of Chemical Physics, Russian Academy of Sciences; Skolkovo Institute of Science and Technology

Email: lyu.yurina@gmail.com
Russian Federation, Moscow; Moscow

M. A. Rosenfeld

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Email: lyu.yurina@gmail.com
Russian Federation, Moscow

References

  1. K. M. Weigandt, N. White, D. Chung, et al., Biophys. J. 103 (11), 2399–2407 (2012). https://doi.org/10.1016/j.bpj.2012.10.036
  2. S. J. Klebanoff, J Leukocyte Biology. 77 (5), 598–625 (2005). https://doi.org/10.1189/jlb.1204697
  3. C. L. Hawkins, D. I. Pattison, M. J. Davies, Amino Acids. 5 (3–4), 259–274 (2003). https://doi.org/10.1007/s00726-003-0016-x
  4. L. V. Yurina, A. D. Vasilyeva, A. E. Bugrova, et al., Dokl. Biochem. Biophys. 484 (1), 37–41 (2019). https://doi.org/10.1134/S1607672919010101
  5. L. V. Yurina, A. D. Vasilyeva, M. I. Indeykina, et al., Free Radical Res. 53( 4), 430–455 (2019). https://doi.org/10.1080/10715762.2019.1600686
  6. A. D. Vasilieva, L. V. Yurina, D. Y. Azarova, et al., Russ. J. Phys. Chem. B 16, 118–122 (2022). https://doi.org/10.1134/S1990793122010316
  7. N. J. White, Y. Wang, X. Fu, et al., Free Rad. Biol. Med. 96, 181–189 (2016). https://doi.org/10.1016/j.freeradbiomed.2016.04.023
  8. W. H. Lau, N. J. White, T. W. Yeo, et al., Sci. Rep. 11(1), 15691 (2021). https://doi.org/10.1038/s41598-021-94401-3
  9. A. N. Shchegolikhin, A. D. Vasilyeva, L. V. Yurina, et al., Russ. J. Phys. Chem. B 15 (1), 123–130 (2021). https://doi.org/10.1134/S1990793121010279
  10. L. A. Wasserman, L. V. Yurina, A. D. Vasilieva, et al., Russ. J. Phys. Chem. B 15 (6), 1036 (2021). https://doi.org/10.1134/S1990793121060105
  11. E. S. Vasiliev, G. V. Karpov, D. K. Shartava, et al., Russ. J. Phys. Chem. B 16 (3), 388–394 (2022). https://doi.org/10.1134/S1990793122030113
  12. J. W. Weisel, C. Nagaswami, Biophys. J. 63 (1), 111–128 (1992). https://doi.org/10.1016/S0006-3495(92)81594-1
  13. J. Kaufmanova, J. Stikarova, A. Hlavackova, et al., Antioxidants 10 (6), 923 (2021). https://doi.org/10.3390/antiox10060923
  14. D. V. Sakharov, J. F. Nagelkerke, D. C. Rijken, J. Biol. Chem. 271 (4), 2133–2138 (1996). https://doi.org/10.1074/jbc.271.4.2133
  15. I. Pechik, J. Madrazo, M. W. Mosesson, et al., Proc. Natl. Acad. Sci. U.S.A. 101 (9), 2718–2723 (2004). https://doi.org/10.1073/pnas.0303440101
  16. J. W. Weisel, R. I. Litvinov, Fibrous Proteins: Struct. Mechan. Cham: Springer International Publishing, 82, 405–456 (2017). https://doi.org/10.1007/978-3-319-49674-0_13
  17. L. Medved, J. W. Weisel, Thromb Haemost. 122 (8), 1265–1278 (2022). https://doi.org/10.1055/a-1719-5584

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Schematic representation of fibrinogen polypeptide chains with modification sites marked.

Download (140KB)
Indexing metadata
3. Fig. 2. Representative curves of thrombin-catalyzed fibrin polymerization (a) and fibrinolysis (b) at the following [HOCl] values ​​in μM: 1 – 0, 2 – 10, 3 – 25, 4 – 50, 5 – 100.

Download (151KB)
Indexing metadata
4. Fig. 3. Changes in the static structure of the fibrin clot (left column; at HOCl concentrations of 0, 10, 25, 50 μM) and the dynamics of plasmin(ogen) distribution during fibrinolysis (columns 2–4).

Download (191KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences