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  • Title: Mathematical model of a network of interaction between p53 and Bcl-2 during genotoxic-induced apoptosis.
    Author: Dogu Y, Díaz J.
    Journal: Biophys Chem; 2009 Jul; 143(1-2):44-54. PubMed ID: 19395147.
    Abstract:
    Ionizing radiation like UV light, gamma and X rays, can produce genotoxic damage in fibroblast cells. This injury can be reverted by activation of specific nuclear molecules. However, intense genotoxic damage induces the activation of the p53 dependent apoptotic pathway. Activated nuclear p53 has the role of a transcription factor that switches on the transcription of the Puma protein, which once released into the cytoplasm leads to the activation of a network of chemical processes that produces cell death. This network is built up with the chemical interaction between pro-apoptotic p53, Puma and Bax proteins and the anti-apoptotic Bcl2 and Bcl-x(L) proteins. In this work we present a mathematical model of this modular network under different regimes of Puma release into the cytoplasm. In this model we use a set of coupled nonlinear differential equations, which is solved by numerical methods, to determine the nature of the equilibrium points of the dynamical system. With this information we construct the phase portrait associated with Puma induced apoptosis and we found that once the genotoxic injury is produced, Bax levels continuously increase. In this work we propose that a possible mechanism for the control of apoptosis is the Bax level in the cytoplasm, i.e., Bax is continuously released into the cytoplasm, even in absence of Puma, according to the kinetic properties of the set of chemical interactions in which the Bcl2/Bax complex takes part. If the damage is reverted before the Bax level reaches a threshold value the apoptotic process is stopped, otherwise the process goes on until cell death.
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