Study on cell apoptosis based on bifurcation and sensitivity analysis

Ying Jiang; Min Luo; Jianfeng Jiao; Ruiqi Wang; Ying Jiang; Min Luo; Jianfeng Jiao; Ruiqi Wang

doi:10.3934/mbe.2019161

Mathematical Biosciences and Engineering

2019, Volume 16, Issue 5: 3235-3250. doi: 10.3934/mbe.2019161

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Research article Special Issues

Study on cell apoptosis based on bifurcation and sensitivity analysis

Department of Mathematics, Shanghai University, Shanghai 200444, P. R. China

Received: 31 December 2018 Accepted: 03 April 2019 Published: 15 April 2019

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, ampli?er, 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 speci?c parameters determine the network functions. More exactly, the activity of BH3 plays a more important role in the initiator module and triggers the ampli?er 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.
- apoptosis,
- sensitivity analysis,
- intrinsic pathway,
- bifurcation
Citation: Ying Jiang, Min Luo, Jianfeng Jiao, Ruiqi Wang. Study on cell apoptosis based on bifurcation and sensitivity analysis[J]. Mathematical Biosciences and Engineering, 2019, 16(5): 3235-3250. doi: 10.3934/mbe.2019161

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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, ampli?er, 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 speci?c parameters determine the network functions. More exactly, the activity of BH3 plays a more important role in the initiator module and triggers the ampli?er 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.

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