C-Papers


论文题名
Bcl-2蛋白抑制钙信号的建模与全局动力学分析
Title
Modeling of Bcl-2 protein suppressed calcium signaling and its global dynamics analysis
作者
牛帅;帅建伟;祁宏
Institution
[牛帅] 山西大学复杂系统研究所;[祁宏] 山西大学复杂系统研究所;[帅建伟] 厦门大学物理系
期刊名称
物理学报
CN
ISSN
1000-3290
出版日期
2017-12-05
Volume
66
Issue
23
YM
238701-
GJZ
Bcl-2 protein; Bifurcation analysis; Calcium signaling
Keywords
Bcl-2 protein; calcium signaling; bifurcation analysis
LWZY
钙离子(Ca~(2+))是生物体内一种生死攸关的信号分子,Bcl-2蛋白可以直接或间接调节IP_3R通道释放Ca~(2+)的能力,借此决定细胞命; 运.本文基于新近的实验成果,针对Bcl-2蛋白间接调控Ca~(2+)的信号通路建立数学模型,得到了与实验数据相符合的结果,从理论上证明了Bcl-; 2蛋白对钙信号有抑制作用.在对模型进行鲁棒性检验之后,本文对该信号通路中一些关键组分的作用进行了预测.以[IP_3]和[Bcl-2]为双分岔参数; 分析的结果表明Bcl-2对刺激强度能产生Ca~(2+)振荡的区域有重要影响.以蛋白磷酸酶1[PP1]和蛋白激酶A[PKA]为单分岔参数分析的结果; 揭示:PP1可以有效地抑制钙信号,而PKA对钙信号的促进作用有一定的局限性.模型结果表明,不同浓度组合的IP_3,Bcl-2和PKA会对钙信号发; 挥复杂的调控作用.本文不仅对相关生物学实验有一定的指导作用,而且可为治疗因钙信号失调而导致的疾病提供思路.
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.
Ref
Fund_Code
National Natural Science Foundation of China [11504214, 31370830,; 11675134]
FileName
10.7498/aps.66.238701

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