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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

Oxygen concentration dependence of rate of autoxidation of oxy-ferrous neuroglobin. Reaction rates observed at various concentrations of oxygen are shown (points) together with the best fit line of the data to an autoxidation scheme involving both inner sphere and outer sphere processes. Error bars represent the range of rates measured in triplicate.
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ijms-16-20082-f002: Oxygen concentration dependence of rate of autoxidation of oxy-ferrous neuroglobin. Reaction rates observed at various concentrations of oxygen are shown (points) together with the best fit line of the data to an autoxidation scheme involving both inner sphere and outer sphere processes. Error bars represent the range of rates measured in triplicate.

Mentions: If a small volume of concentrated, DTT reduced, neuroglobin is rapidly mixed with a large volume of oxygenated buffer a transient oxygenated species is produced which then undergoes oxidation to the ferric form over a period of minutes. The oxidation process follows a simple exponential time course. However the concentration dependence of the rate of the oxidation process follows a non-linear pattern (Figure 2).


A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature.

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

Oxygen concentration dependence of rate of autoxidation of oxy-ferrous neuroglobin. Reaction rates observed at various concentrations of oxygen are shown (points) together with the best fit line of the data to an autoxidation scheme involving both inner sphere and outer sphere processes. Error bars represent the range of rates measured in triplicate.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-20082-f002: Oxygen concentration dependence of rate of autoxidation of oxy-ferrous neuroglobin. Reaction rates observed at various concentrations of oxygen are shown (points) together with the best fit line of the data to an autoxidation scheme involving both inner sphere and outer sphere processes. Error bars represent the range of rates measured in triplicate.
Mentions: If a small volume of concentrated, DTT reduced, neuroglobin is rapidly mixed with a large volume of oxygenated buffer a transient oxygenated species is produced which then undergoes oxidation to the ferric form over a period of minutes. The oxidation process follows a simple exponential time course. However the concentration dependence of the rate of the oxidation process follows a non-linear pattern (Figure 2).

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