Interactions among oscillatory pathways in NF-kappa B signaling.
Interactions among oscillatory pathways in NF-kappa B signaling.
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NF-kappa B信号传导中振荡途径之间的相互作用。
DOI：
10.1186/1752-0509-5-23
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发表时间：
2011-02-03
影响因子：
--
通讯作者：
Muldoon MR
中科院分区：
文献类型：
--
作者：
Wang Y;Paszek P;Horton CA;Kell DB;White MR;Broomhead DS;Muldoon MR
肿瘤坏死因子α（TNF-α）的持续刺激诱导核因子κ B（NF-κ B）系统中的大量振荡-在单细胞和群体水平均观察到。尽管其机制尚未完全阐明，但已确定了一个核心系统，该系统由涉及NF-κ B B（RelA：p50异源二聚体）及其抑制剂I-κ B-α的负反馈环组成。许多作者建议，这个核心振荡器应该耦合到其他振荡路径。首先，我们分析单细胞数据的实验中，NF-κ B系统是被迫短列车强脉冲的TNF-α。NF-κ B的核质浓度比的功率谱表明细胞的响应被脉冲频率所夹带。使用Caroline Horton的NF-κ B系统的最新模型，我们进行了广泛的数值模拟，以分析具有宽范围频率和振幅的TNF-α刺激脉冲序列诱导的响应频率。这些研究表明，对于足够弱的刺激，各种非线性共振应该是可观察的。为了进一步探索探测替代反馈机制的可能性，我们还将模型耦合到具有广泛强度和频率的正弦信号。我们的研究结果表明，至少在模拟中，频率以外的强迫和主要的NF-κ B振荡器可以激发通过次和超谐波共振，产生准周期，甚至混沌动力学。我们的数值结果表明，在脉冲刺激实验中观察到的夹带现象是高强度的刺激的结果。基于当前模型的计算研究表明，对于足够弱的刺激，周期性脉动强迫和系统的固有频率之间的共振相互作用可能变得明显。进一步的模拟表明，NF-κ B反馈振子的非线性意味着即使是正弦调制的强迫也可以引起丰富多样的非线性相互作用。
Sustained stimulation with tumour necrosis factor alpha (TNF-alpha) induces substantial oscillations—observed at both the single cell and population levels—in the nuclear factor kappa B (NF-kappa B) system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer) and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways. First we analyse single-cell data from experiments in which the NF-kappa B system is forced by short trains of strong pulses of TNF-alpha. Power spectra of the ratio of nuclear-to-cytoplasmic concentration of NF-kappa B suggest that the cells' responses are entrained by the pulsing frequency. Using a recent model of the NF-kappa B system due to Caroline Horton, we carried out extensive numerical simulations to analyze the response frequencies induced by trains of pulses of TNF-alpha stimulation having a wide range of frequencies and amplitudes. These studies suggest that for sufficiently weak stimulation, various nonlinear resonances should be observable. To explore further the possibility of probing alternative feedback mechanisms, we also coupled the model to sinusoidal signals with a wide range of strengths and frequencies. Our results show that, at least in simulation, frequencies other than those of the forcing and the main NF-kappa B oscillator can be excited via sub- and superharmonic resonance, producing quasiperiodic and even chaotic dynamics. Our numerical results suggest that the entrainment phenomena observed in pulse-stimulated experiments is a consequence of the high intensity of the stimulation. Computational studies based on current models suggest that resonant interactions between periodic pulsatile forcing and the system's natural frequencies may become evident for sufficiently weak stimulation. Further simulations suggest that the nonlinearities of the NF-kappa B feedback oscillator mean that even sinusoidally modulated forcing can induce a rich variety of nonlinear interactions.
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DOI：
10.1006/bbrc.2000.2786
发表时间：
2000-06-07
影响因子：
3.1
作者：
Ikeda, A;Sun, XG;Yamamoto, K
通讯作者：
Yamamoto, K
DOI：
10.1073/pnas.0610759104
发表时间：
2007-04-17
影响因子：
11.1
作者：
Pigolotti, Simone;Krishna, Sandeep;Jensen, Mogens H.
通讯作者：
Jensen, Mogens H.
DOI：
10.1073/pnas.93.13.6721
发表时间：
1996-06-25
影响因子：
11.1
作者：
Song, HY;Rothe, M;Goeddel, DV
通讯作者：
Goeddel, DV
脉冲刺激决定了NF-kappab依赖性转录的时间和特异性。
DOI：
10.1126/science.1164860
发表时间：
2009-04-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ashall L;Horton CA;Nelson DE;Paszek P;Harper CV;Sillitoe K;Ryan S;Spiller DG;Unitt JF;Broomhead DS;Kell DB;Rand DA;Sée V;White MR
通讯作者：
White MR
影响因子：
56.9
作者：
Hoffmann, A;Levchenko, A;Baltimore, D
通讯作者：
Baltimore, D