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A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature

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 ne...

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Detalles Bibliográficos
Autores principales: Liu, Anyang, Brittain, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581342/
https://www.ncbi.nlm.nih.gov/pubmed/26305249
http://dx.doi.org/10.3390/ijms160820082
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author Liu, Anyang
Brittain, Thomas
author_facet Liu, Anyang
Brittain, Thomas
author_sort Liu, Anyang
collection PubMed
description 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.
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spelling pubmed-45813422015-09-28 A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature Liu, Anyang Brittain, Thomas Int J Mol Sci Article 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. MDPI 2015-08-24 /pmc/articles/PMC4581342/ /pubmed/26305249 http://dx.doi.org/10.3390/ijms160820082 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Anyang
Brittain, Thomas
A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature
title A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature
title_full A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature
title_fullStr A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature
title_full_unstemmed A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature
title_short A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature
title_sort futile redox cycle involving neuroglobin observed at physiological temperature
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581342/
https://www.ncbi.nlm.nih.gov/pubmed/26305249
http://dx.doi.org/10.3390/ijms160820082
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