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Mathematical Model of Platelet Intracellular Signaling After Activation by Fucoidan

  • A. A. MartyanovEmail author
  • F. A. Balabin
  • A. S. Maiorov
  • E. V. Shamova
  • M. A. Panteleev
  • A. N. Sveshnikova
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Abstract

Blood platelets are the cells responsible for prevention of the blood loss. Fucoidan is a brown algae extract that is known to activate platelets via C-type lectin receptor of the second type. On the other hand, different fucoidans are now considered as perspective immunomodulators. Thus, application of fucoidan as a medicinal drug seems to be contradictory. In this work we studied activation of platelets by fucoidan in silico and in vitro. The computational model describes the behavior of the participants of the fucoidan receptor signaling cascade. The model was validated with available experimental data published earlier. In order to confirm the model predictions, the fucoidan-induced activation of platelets was assessed in flow cytometry and aggregometry experiments. The resultant model describes changes in the activity of tyrosine kinases of Syk and Sarc family and subsequent activation of phospholipase Cγ2. One of the main model prediction is a significant increase in the platelet cytosolic calcium level after the activation by fucoidan. This prediction was confirmed in the experiments. Thus, fucoidan, as a true platelet activator, cannot be applied in therapy.

Keywords:

intracellular signaling computer modeling flow cytometry 

Notes

ACKNOWLEDGMENTS

Authors are grateful to Prof. F.I. Ataullakhanov for valuable discussions and advise during the research process, as well as to Dr. N.E. Ustyuzhanina for discussions concerning fucoidan.

The work was supported by the Russian Foundation for Basic Research (project no. 17-54-04009), Belorussian Foundation for Basic Research (project no. B17RM-006), and by the President’s grants for young investigators (project nos. MK-5879.2016.4 and MD-229.2017.4).

COMPLIANCE WITH ETHICAL STANDARDS

Conflict of interests. The authors declare that they have no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • A. A. Martyanov
    • 1
    • 2
    • 3
    Email author
  • F. A. Balabin
    • 1
  • A. S. Maiorov
    • 1
    • 2
    • 3
  • E. V. Shamova
    • 4
  • M. A. Panteleev
    • 1
    • 2
    • 3
  • A. N. Sveshnikova
    • 1
    • 2
    • 3
  1. 1.Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of SciencesMoscowRussia
  2. 2.Faculty of Physics, Moscow Lomonosov State UniversityMoscowRussia
  3. 3.National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology named after Dmitry RogachevMoscowRussia
  4. 4.Belarusian State University, Faculty of Physics, Department of BiophysicsMinskBelarus

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