Previous studies identifying the potential anti-apoptotic role of
neuroglobin raise the question as to how cells might employ
neuroglobin to avoid the apoptotic impact of acute
hypoxia whilst also avoiding chronic enhancement of tumour formation. We show that under likely physiological conditions
neuroglobin can take part in a futile redox cycle. Determination of the rate constants for each of the steps in the cycle allows us to mathematically model the steady state concentration of the active anti-apoptotic ferrous form of
neuroglobin under various conditions. Under likely normal physiological conditions
neuroglobin is shown to be present in the ferrous state at approximately 30% of its total cellular concentration. Under hypoxic conditions this rapidly rises to approximately 80%. Temporal analysis of this model indicates that the transition from low concentrations to high concentration of ferrous
neuroglobin occurs on the seconds time scale. These findings indicate a potential control model for the anti-apoptotic activity of
neuroglobin, under likely physiological conditions, whereby, in normoxic conditions, the anti-apoptotic activity of
neuroglobin is maintained at a low level, whilst immediately a transition occurs to a hypoxic situation, as might arise during
stroke, the anti-apoptotic activity is drastically increased. In this way the cell avoids unwanted increased oncogenic potential under normal conditions, but the rapid activation of
neuroglobin provides anti-apoptotic protection in times of acute
hypoxia.