Advertisement

In Silico Modeling and Simulation Approach for Apoptosis Caspase Pathways

  • Pedro Pablo González-Pérez
  • Maura Cárdenas-García
Conference paper
Part of the Advances in Intelligent Systems and Computing book series (AISC, volume 803)

Abstract

We revisit and improve in silico modeling and simulation approach of the apoptosis caspases pathways, initially developed for exploring and discovering the complex interaction patterns of apoptotic caspases and the mitochondrial role. Symbolic abstractions and algorithms of the in silico model were improved to allow dealing with crucial aspects of the cellular signal transduction such as cellular processes. Also, the particular model of extrinsic and intrinsic apoptotic signaling pathways was improved, increasing the number of reactions and using all kinetic parameters accurately calculated. Using the computational simulation tool BTSSOC-Cellulat, we were able to determine experimentally how the modulation of concentrations of proteins XIAP, cFLIPs and TRAIL/FASL, can cause the death of cancerous cells. Our results show how crucial were the improvements made in the in silico modeling approach, which in turn were reflected in the accuracy of the simulation and, therefore, in the significant value of the in silico experiments carried out.

Keywords

Caspase signaling pathway Apoptosis In silico modeling and simulation approach In silico experiments 

References

  1. 1.
    Kerr, J.F.T., Wyllie, A.H., Currie, A.R.: Apoptosis: a basic biological phenomenon with wide-ranging implication in tissue kinetics. Br. J. Cancer 26(4), 239–257 (1972)CrossRefGoogle Scholar
  2. 2.
    Wyllie, A.H.: Apoptosis: an overview. Br. Med. Bull. 53(3), 451–465 (1997)CrossRefGoogle Scholar
  3. 3.
    Poreba, M., Szalek, A., Kasperkiewicz, P., Rut, W., Salvesen, G.S., Drag, M.: Small molecule active site directed tools for studying human caspases. Chem. Rev. 115(22), 12546–12629 (2015).  https://doi.org/10.1021/acs.chemrev.5b00434CrossRefGoogle Scholar
  4. 4.
    Danial, N.N., Korsmeyer, S.J.: Cell death: critical control points. Cell 116(2), 205–219 (2004).  https://doi.org/10.1016/S0092-8674(04)00046-7CrossRefGoogle Scholar
  5. 5.
    Poreba, M., Strózyk, A., Salvesen, G.S., Drag, M.: Caspase substrates and inhibitors. Cold Spring Harb. Perspect. Biol. 5(8), a008680 (2013).  https://doi.org/10.1101/cshperspect.a008680CrossRefGoogle Scholar
  6. 6.
    Songane, M., Khair, M., Saleh, M.: An update view on the function of caspases in inflammation and immunity. Semin. Cell Dev. Biol. (2018).  https://doi.org/10.1016/j.semcdb.2018.01.001
  7. 7.
    Alves, R., Antunes, F., Salvador, A.: Tools for kinetic modeling of biochemical networks. Nat. Biotechnol. 24(6), 667–672 (2006).  https://doi.org/10.1038/nbt0606-667CrossRefGoogle Scholar
  8. 8.
    Ciocchetta, F., Duguid, A., Guerriero, M.L.: A compartmental model of the cAMP/PKA/MAPK pathway in bio-PEPA. In: Third Workshop on Membrane Computing and Biologically Inspired Process Calculi (MeCBIC) (2009). http://dx.doi.org/10.4204/EPTCS.11.5
  9. 9.
    Kerr, R.A., Bartol, T.M., Kaminsky, B., Dittrich, M., Chang, J.C., Baden, S.B., Sejnowski, T.J., Stiles, J.R.: Fast Monte Carlo simulation methods for biological reaction-diffusion systems in solution and on surfaces. SIAM J. Sci. Comput. 30(36), 3126–3149 (2008).  https://doi.org/10.1137/070692017MathSciNetCrossRefzbMATHGoogle Scholar
  10. 10.
    Hoops, S., et al.: COPASI: a complex pathway simulator. Bio-informatics 22(24), 3067–3074 (2006).  https://doi.org/10.1093/bioinformatics/btl485CrossRefGoogle Scholar
  11. 11.
    Cowan, A.E., Moraru, I.I., Schaff, J.C., Slepchenko, B.M., Loew, L.M.: Spatial modeling of cell signaling networks. Methods Cell Biol. 110, 195–221 (2012).  https://doi.org/10.1016/B978-0-12-388403-9.00008-4CrossRefGoogle Scholar
  12. 12.
    Swat, M., Thomas, G.L., Belmonte, J.M., Shirinifard, A., Hmeljak, D., Glazier, J.A.: Multi-scale modeling of tissues using CompuCell 3D. Methods Cell Biol. 110, 325–366 (2012).  https://doi.org/10.1016/b978-0-12-388403-9.00013-8CrossRefGoogle Scholar
  13. 13.
    Martinou, J.C., Youle, R.J.: Mitochondria in apoptosis; Bcl-2 family members and mitochondrial dynamics. Dev. Cell 21(1), 92–101 (2011).  https://doi.org/10.1016/j.devcel.2011.06.017CrossRefGoogle Scholar
  14. 14.
    González-Pérez, P.P., Omicini, A., Sbaraglia, M.: A biochemically inspired coordination-based model for simulating intracellular signalling pathway. J. Simul. 27(3), 216–226 (2013).  https://doi.org/10.1057/jos.2012.28CrossRefGoogle Scholar
  15. 15.
    Cárdenas-García, M., González-Pérez, P.P., Montagna, S., Cortés Sánchez, O., Caballero, E.H.: Modeling intercellular communication as a survival strategy of cancer cells: an in silico approach on a flexible bioinformatics framework. Bioinf. Biol. Insights 10, 5–18 (2016).  https://doi.org/10.4137/BBI.S38075CrossRefGoogle Scholar
  16. 16.
    Gelernter, D.: Generative communication in Linda. ACM Trans. Program. Lang. Syst. 7(1), 80–112 (1985).  https://doi.org/10.1145/2363.2433CrossRefzbMATHGoogle Scholar
  17. 17.
    Gillespie, D.T.: Exact stochastic simulation of coupled chemical reactions. J. Phys. Chem. 81(25), 2340–2361 (1977).  https://doi.org/10.1021/j100540a008CrossRefGoogle Scholar
  18. 18.
    Cárdenas-García, M., González-Pérez, P.P., Montagna, S.: bioinformatics. EMBnet.journal 18(S18.B), 94–96 (2012). Special Issue NETTAB 2012 Workshop on “Integrated Bio-Search”. http://dx.doi.org/10.14806/ej.18.B.563
  19. 19.
    Cárdenas-García, M., González-Pérez, P.P.: Applying the tuple space-based approach to the simulation of the caspases, an essential signalling pathway. J. Integr. Bioinf. 10(1), 225.  https://doi.org/10.2390/biecoll-jib-2013-225. ISSN 1613-4516
  20. 20.
    Kang, W., et al.: Structural and biochemical basis for the inhibition of cell death by APIP, a methionine salvage enzyme. Proc. Nat. Acad. Sci. 111(1), E54–E61 (2014).  https://doi.org/10.1073/pnas.1308768111CrossRefGoogle Scholar
  21. 21.
    Karki, P., Lee, J., Shin, S.Y., Cho, B., Park, I.S.: Kinetic comparison of procaspase-3 and caspase-3. Arch. Biochem. Biophys. 442(1), 125–132 (2005).  https://doi.org/10.1016/j.abb.2005.07.023CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Pedro Pablo González-Pérez
    • 1
  • Maura Cárdenas-García
    • 2
  1. 1.Universidad Autónoma MetropolitanaCiudad de MéxicoMexico
  2. 2.Benemérita Universidad Autónoma de PueblaPueblaMexico

Personalised recommendations