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Study on cell apoptosis based on bifurcation and sensitivity analysis


Pages: --, Volume 16, Issue 5, 2019

doi:

Abstract: Apoptosis plays critical roles in embryonic development and adult tissue homeostasis. It has been shown that several feedback loops regulate the intrinsic pathway of apoptosis, however, it remains elusive how they coordinately modulate apoptosis. For the three modules (initiator, amplifier, and executioner) of the intrinsic pathway, we mainly study dynamics of the initiator and the executioner modules. In this paper, we aim to identify important regulatory processes in apoptosis through bifurcation and single-parameter sensitivity analysis. We find that modules or feedback loops but not detailed parameter values determine the network functions. More exactly, we find that the activity of BH3 plays a more important role in the initiator module and triggers the amplifier module. In addition, aC9 autocrine expression and C9/XIAP feedback loop is more sensitive in executioner module. We also find that three feedback loops respectively including BH3AC/BH3DR, MDM2/ARF/ASPP, and p53helper/p53killer play more important roles in cell fate decisions after DNA damage. Our research provides a rational basis for the design of clinical trials of anticancer drugs.


Keywords: Apoptosis; sensitivity analysis; intrinsic pathway; bifurcation
Mathematics Subject Classification:  

Received: July 2004; Revised: August 2004; Published: November 2004.