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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 dynamics response of the neuroglobin redox cycle to rapid changes in oxygen concentration. The response, in the change of the level of the various forms of neuroglobin present in the redox cycle, to a rapid change in oxygen concentration from a fixed value of 50 μM to a fixed value of 2 μM is shown, as determined employing the redox cycling model. The hexa co-ordinate ferrous form is indicated by the closed circles; the ferric form by the descending line; the oxygenated form by the open circles and the penta co-ordinated ferrous form by the open squares (running along the x axis). A reduction rate of 0.015 s−1 was employed in these calculations and a total neuroglobin concentration of 5 μM.
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ijms-16-20082-f004: Simulation of the dynamics response of the neuroglobin redox cycle to rapid changes in oxygen concentration. The response, in the change of the level of the various forms of neuroglobin present in the redox cycle, to a rapid change in oxygen concentration from a fixed value of 50 μM to a fixed value of 2 μM is shown, as determined employing the redox cycling model. The hexa co-ordinate ferrous form is indicated by the closed circles; the ferric form by the descending line; the oxygenated form by the open circles and the penta co-ordinated ferrous form by the open squares (running along the x axis). A reduction rate of 0.015 s−1 was employed in these calculations and a total neuroglobin concentration of 5 μM.

Mentions: Employing the same modelling principles it was possible to investigate the dynamic response of the redox cycle system to rapid changes in oxygen concentration such as might be encountered in the transition from normoxic to ischemic situations. It was found that the system is capable of very significant changes in the concentration of the anti-apoptotic form of neuroglobin in a fraction of a second (Figure 4).


A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature.

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

Simulation of the dynamics response of the neuroglobin redox cycle to rapid changes in oxygen concentration. The response, in the change of the level of the various forms of neuroglobin present in the redox cycle, to a rapid change in oxygen concentration from a fixed value of 50 μM to a fixed value of 2 μM is shown, as determined employing the redox cycling model. The hexa co-ordinate ferrous form is indicated by the closed circles; the ferric form by the descending line; the oxygenated form by the open circles and the penta co-ordinated ferrous form by the open squares (running along the x axis). A reduction rate of 0.015 s−1 was employed in these calculations and a total neuroglobin concentration of 5 μM.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-20082-f004: Simulation of the dynamics response of the neuroglobin redox cycle to rapid changes in oxygen concentration. The response, in the change of the level of the various forms of neuroglobin present in the redox cycle, to a rapid change in oxygen concentration from a fixed value of 50 μM to a fixed value of 2 μM is shown, as determined employing the redox cycling model. The hexa co-ordinate ferrous form is indicated by the closed circles; the ferric form by the descending line; the oxygenated form by the open circles and the penta co-ordinated ferrous form by the open squares (running along the x axis). A reduction rate of 0.015 s−1 was employed in these calculations and a total neuroglobin concentration of 5 μM.
Mentions: Employing the same modelling principles it was possible to investigate the dynamic response of the redox cycle system to rapid changes in oxygen concentration such as might be encountered in the transition from normoxic to ischemic situations. It was found that the system is capable of very significant changes in the concentration of the anti-apoptotic form of neuroglobin in a fraction of a second (Figure 4).

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