Slaby Oliver, Lebiedz Dirk
Center for Systems Biology, Freiburg, Germany.
Biophys J. 2009 Jan;96(2):417-28. doi: 10.1016/j.bpj.2008.09.044.
The group of Howard Petty has claimed exotic metabolic wave phenomena together with mutually phase-coupled NAD(P)H- and calcium-oscillations in human neutrophils. At least parts of these phenomena are highly doubtful due to extensive failure of reproducibility by several other groups and hints that unreliable data from the Petty lab are involved in publications concerning circular calcium waves. The aim of our theoretical spatiotemporal modeling approach is to propose a possible and plausible biochemical mechanism which would, in principle, be able to explain metabolic oscillations and wave phenomena in neutrophils. Our modeling suggests the possibility of a calcium-controlled glucose influx as a driving force of metabolic oscillations and a potential role of polarized cell geometry and differential enzyme distribution for various NAD(P)H wave phenomena. The modeling results are supposed to stimulate further controversial discussions of such phenomena and potential mechanisms and experimental efforts to finally clarify the existence and biochemical basis of any kind of temporal and spatiotemporal patterns of calcium signals and metabolic dynamics in human neutrophils. Independent of Petty's observations, they present a general feasibility study of such phenomena in cells.
霍华德·佩蒂团队宣称在人类中性粒细胞中发现了奇异的代谢波现象以及相互相位耦合的NAD(P)H和钙振荡。由于其他几个团队广泛无法重复这些现象,并且有迹象表明佩蒂实验室的不可靠数据涉及有关环形钙波的出版物,所以这些现象中至少部分是高度可疑的。我们理论时空建模方法的目的是提出一种可能且合理的生化机制,原则上该机制能够解释中性粒细胞中的代谢振荡和波现象。我们的建模表明,钙控制的葡萄糖内流有可能作为代谢振荡的驱动力,并且极化细胞几何形状和不同的酶分布对于各种NAD(P)H波现象可能具有潜在作用。建模结果旨在激发对此类现象和潜在机制的进一步争议性讨论,以及为最终阐明人类中性粒细胞中钙信号和代谢动力学的任何时间和时空模式的存在及生化基础所做的实验努力。独立于佩蒂的观察结果,这些结果展示了此类现象在细胞中的一般可行性研究。