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A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature.

Liu A, Brittain T - Int J Mol Sci (2015)

Bottom Line: 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.Temporal analysis of this model indicates that the transition from low concentrations to high concentration of ferrous neuroglobin occurs on the seconds time scale.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.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand. a.liu@auckland.ac.nz.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Simulation of the steady state level of ferrous neuroglobin present during redox cycling. The three dimensional surface represents the calculated steady-state level of ferrous neuroglobin present under different conditions of oxygen concentration and reduction rate constant determined from the redox cycling model. The oxygen concentrations plotted in the graph are the initial concentrations, which were maintained throughout the simulations.
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ijms-16-20082-f003: Simulation of the steady state level of ferrous neuroglobin present during redox cycling. The three dimensional surface represents the calculated steady-state level of ferrous neuroglobin present under different conditions of oxygen concentration and reduction rate constant determined from the redox cycling model. The oxygen concentrations plotted in the graph are the initial concentrations, which were maintained throughout the simulations.

Mentions: Having obtained the rate constants for all of the steps involved in the putative redox cycle for neuroglobin (see Table 1) it was then possible to investigate the impact of independently varying the oxygen concentration and reduction rate in the simulation model on the steady state level of the anti-apoptotic form of neuroglobin (Figure 3). The steady state level of the anti-apoptotic ferrous forms was found to be sensitive to the oxygen concentration in the range likely to be experienced between normoxic and ischemic conditions. On the other hand, the level was found to be relatively insensitive to the reduction rate for ferric neuroglobin over the likely range.


A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature.

Liu A, Brittain T - Int J Mol Sci (2015)

Simulation of the steady state level of ferrous neuroglobin present during redox cycling. The three dimensional surface represents the calculated steady-state level of ferrous neuroglobin present under different conditions of oxygen concentration and reduction rate constant determined from the redox cycling model. The oxygen concentrations plotted in the graph are the initial concentrations, which were maintained throughout the simulations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581342&req=5

ijms-16-20082-f003: Simulation of the steady state level of ferrous neuroglobin present during redox cycling. The three dimensional surface represents the calculated steady-state level of ferrous neuroglobin present under different conditions of oxygen concentration and reduction rate constant determined from the redox cycling model. The oxygen concentrations plotted in the graph are the initial concentrations, which were maintained throughout the simulations.
Mentions: Having obtained the rate constants for all of the steps involved in the putative redox cycle for neuroglobin (see Table 1) it was then possible to investigate the impact of independently varying the oxygen concentration and reduction rate in the simulation model on the steady state level of the anti-apoptotic form of neuroglobin (Figure 3). The steady state level of the anti-apoptotic ferrous forms was found to be sensitive to the oxygen concentration in the range likely to be experienced between normoxic and ischemic conditions. On the other hand, the level was found to be relatively insensitive to the reduction rate for ferric neuroglobin over the likely range.

Bottom Line: 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.Temporal analysis of this model indicates that the transition from low concentrations to high concentration of ferrous neuroglobin occurs on the seconds time scale.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.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand. a.liu@auckland.ac.nz.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus