系统方法分析NF-κB信号转导网络产生持续振荡的条件

A Systematic Approach in Analyzing Sustained Oscillations in An NF-κB Signal Transduction Pathway System

振荡现象在生物系统中普遍存在,研究振荡现象对进一步了解细胞网络的基因调节功能具有重要意义。与实验研究相结合的系统分析方法为生物网络的振荡行为提供了新的研究途径。NF-κB是免疫应答、炎症反应和机体发育过程中的关键转录因子,近年的实验和计算研究揭示了细胞核内NF-κB浓度的衰减振荡现象。该文基于NF-κB信号转导网络的常微分方程数学模型,采用分岔分析方法研究分岔参数变化对系统振荡特性的影响,主要研究了系统能否产生等幅的持续振荡(又称极限环振荡)及其产生条件。经过系统化的单参数和双参数分岔分析发现:NF-κB在细胞核内的浓度能够在一定条件下产生极限环振荡,模型计算给出了产生极限环振荡的关键参数的范围。

Oscillation phenomenon is very common in biological systems.It is crucial to study oscillatory behaviors to understand gene regulation functions.Model-based analysis in combination with experimental study provides a new and systematic way to investigate biological oscillations.The nuclear factor-κB（NF-κB） signaling is an important signaling pathway that is involved in a variety of cellular processes including immune response,inflammation,and apoptosis.Recent studies revealed damped oscillations of NF-κB activity both experimentally and computationally,etc.In this work,based on a differential equation model,bifurcation analysis was used to examine whether it was possible for this system to produce sustained oscillations（limit cycle oscillations） rather than damped oscillations.Both one-and two-parameter bifurcation analyses have been performed and it was found that certain conditions could possibly result in sustained oscillations of nuclear NF-κB activity.The parameter regimes corresponding to such oscillations were calculated with this method.