A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature
| Autor: | Anyang Liu, Thomas Brittain |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Redox cycle
Apoptosis Nerve Tissue Proteins Biology Models Biological Article Catalysis Body Temperature lcsh:Chemistry modelling Inorganic Chemistry Acute hypoxia Humans Globin Physical and Theoretical Chemistry lcsh:QH301-705.5 Molecular Biology Spectroscopy Volume concentration High concentration Normal conditions Organic Chemistry General Medicine Cell Hypoxia Tumor formation Globins Computer Science Applications Cell biology neuroglobin Gene Expression Regulation lcsh:Biology (General) lcsh:QD1-999 Neuroglobin oxygenation Oxidation-Reduction |
| Zdroj: | International Journal of Molecular Sciences Volume 16 Issue 8 Pages 20082-20094 International Journal of Molecular Sciences, Vol 16, Iss 8, Pp 20082-20094 (2015) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms160820082 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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