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Modelling toxin effects on protein biosynthesis in eukaryotic cells.

Vladas Skakauskas1, Pranas Katauskis1

  • 1Faculty of Mathematics and Informatics, Vilnius University, Naugarduko 24, 03225 Vilnius, Lithuania.

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|June 10, 2017
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Summary

This study models ricin toxin's inhibition of protein synthesis in eukaryotic cells and how antibodies targeting the RTB subunit can reduce its toxic effects, offering insights into cellular defense mechanisms.

Keywords:
AntibodyCell receptorProtein biosynthesisRicin

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Area of Science:

  • Cellular Biology
  • Biochemistry
  • Toxicology

Background:

  • Ricin toxin inhibits eukaryotic protein biosynthesis by inactivating ribosomes.
  • Ricin enters cells via endocytosis and its toxic effects are mediated by the RTA subunit in the cytosol.
  • Antibodies targeting ricin's RTB subunit are a potential therapeutic strategy.

Purpose of the Study:

  • To develop a generic mathematical model for ricin toxin's inhibition of protein biosynthesis.
  • To investigate the reduction of ricin's toxic effects using antibodies against the RTB subunit.
  • To analyze the impact of kinetic parameters on cellular responses and antibody efficacy.

Main Methods:

  • A deterministic ordinary differential equations (ODEs) model was developed.
  • The model simulates toxin endocytosis, exocytosis, lysosomal degradation, and intracellular trafficking.
  • The model incorporates RTA subunit separation, translocation into the cytosol, and ribosome inactivation.

Main Results:

  • The model accurately describes the complex intracellular journey of ricin.
  • It demonstrates how RTA inactivation of ribosomes leads to protein synthesis inhibition.
  • Simulations show the potential of anti-RTB antibodies to mitigate ricin's toxic effects.

Conclusions:

  • The developed model provides a framework for understanding ricin-induced cytotoxicity.
  • Antibody-based interventions targeting the RTB subunit show promise for neutralizing ricin.
  • Further kinetic parameter analysis can optimize therapeutic strategies against ricin poisoning.