关键词: Bcl-2蛋白/
钙信号/
分岔分析
English Abstract
Modeling of Bcl-2 protein suppressed calcium signaling and its global dynamics analysis
Niu Shuai1,2,Shuai Jian-Wei3,
Qi Hong1
1.Complex Systems Research Center, Shanxi University, Taiyuan 030006, China;
2.School of Mathematical Sciences, Shanxi University, Taiyuan 030006, China;
3.Department of Physics, Xiamen University, Xiamen 361005, China
Fund Project:Project supported by the National Natural Science Foundation of China (Grant Nos. 11504214, 31370830, 11675134).Received Date:09 June 2017
Accepted Date:18 July 2017
Published Online:05 December 2017
Abstract:Calcium ion (Ca2+) is a signal for both life and death in cells. Either directly or indirectly, Bcl-2 protein can regulate Ca2+ release from IP3R channel, thereby determining the cell fate. In this work, based on recent experimental results, a mathematical model is constructed to describe the signaling pathway of Ca2+ release regulated by Bcl-2 indirectly. The model output fits nicely to the experimental data. The model demonstrates that Bcl-2 can suppress Ca2+ signaling. After the robustness test of the model, the roles of some key components in the signaling pathway are predicted. Two-parameter bifurcation analyses of[IP3] and [Bcl-2] are conducted to show that Bcl-2 has a crucial role in the oscillatory region of Ca2+ signaling. Single-parameter bifurcation analyses of [PP1] and [PKA] reveal that the PP1 can inhibit Ca2+ from signaling potently, while PKA only promotes Ca2+ signaling to some extent. Our model also indicates that the different combinations of concentrations of IP3, Bcl-2 and PKA generate complex regulations on Ca2+ signaling. This work not only plays a guiding role in relevant biological experiments, but also provides some insights into the treatment of diseases caused by disruption of Ca2+ homeostasis.
Keywords: Bcl-2 protein/
calcium signaling/
bifurcation analysis
