Open AccessStudy on cell apoptosis based on bifurcation and sensitivity analysis
Author(s) -
Ying Jiang,
Moulun Luo,
Jianfeng Jiao,
Ruiqi Wang
Publication year - 2019
Publication title -
mathematical biosciences and engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.451
H-Index - 45
eISSN - 1551-0018
pISSN - 1547-1063
DOI - 10.3934/mbe.2019161
Subject(s) - sensitivity (control systems) , bifurcation , apoptosis , biological system , physics , mathematics , computer science , control theory (sociology) , biology , engineering , artificial intelligence , electronic engineering , nonlinear system , genetics , quantum mechanics , control (management)
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 studied dynamics of the initiator and the executioner modules. In this paper, we aimed to identify important regulatory processes in apoptosis through bifurcation and single-parameter sensitivity analysis. We found that modules or feedback loops but not specific parameters determine the network functions. More exactly, 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 are more sensitive in executioner module. We also found 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.