Pushing arterial-venous plasma biomarkers to new heights: a model for personalised redox metabolomics?
Pushing arterial-venous plasma biomarkers to new heights: a model for personalised redox metabolomics?
The chemical and functional interactions between Reactive Oxygen (ROS), Nitrogen (RNS) and Sulfur (RSS) species allow organisms to detect and respond to metabolic and environmental stressors, such as exercise and altitude exposure. Whether redox markers and constituents of this ‘Reactive Species Interactome’ (RSI) differ in concentration between arterial and venous blood is unknown. We hypothesised that such measurements may provide useful insight into metabolic/redox regulation at the whole-body level and would be consistent between individuals exposed to identical challenges. An exploratory study was performed during the Xtreme Alps expedition in 2010 in which four healthy individuals (2 male, 2 female) underwent paired arterial and central venous blood sampling before, during and after performance of a constant-work-rate cardiopulmonary exercise test, at sea level and again at 4559 m. Unexpectedly, plasma total free thiol and free cysteine concentrations remained substantially elevated at altitude throughout exercise with minimal arteriovenous gradients. Free sulfide concentrations changed only modestly upon combined altitude/exercise stress, whereas bound sulfide levels were lower at altitude than sea-level. No consistent signal indicative of the expected increased oxidative stress and nitrate→nitrite→NO reduction was observed with 4-hydroxynonenal, isoprostanes, nitrate, nitrite, nitroso species and cylic guanosine monophosphate. However, the observed arteriovenous concentration differences revealed a dynamic pattern of response that was unique to each participant. This novel redox metabolomic approach of obtaining quantifiable ‘metabolic signatures’ to a defined physiological challenge could potentially offer new avenues for personalised medicine.
Altitude, Hydrogen sulfide, Hypoxia, Oxidative stress, Oxygen, Thiols
Cumpstey, Andrew F.
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Minnion, Magdalena
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Fernandez, Bernadette
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Mikus-Lelinska, Monika
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Mitchell, Kay
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Martin, Dan S.
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Grocott, Michael
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Feelisch, Martin
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6 February 2019
Cumpstey, Andrew F.
cd040417-5e62-41d2-8640-1ec8905858a7
Minnion, Magdalena
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Fernandez, Bernadette
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Mikus-Lelinska, Monika
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Mitchell, Kay
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Martin, Dan S.
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Grocott, Michael
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Feelisch, Martin
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Cumpstey, Andrew F., Minnion, Magdalena, Fernandez, Bernadette, Mikus-Lelinska, Monika, Mitchell, Kay, Martin, Dan S., Grocott, Michael and Feelisch, Martin
(2019)
Pushing arterial-venous plasma biomarkers to new heights: a model for personalised redox metabolomics?
Redox Biology, 21, [101113].
(doi:10.1016/j.redox.2019.101113).
Abstract
The chemical and functional interactions between Reactive Oxygen (ROS), Nitrogen (RNS) and Sulfur (RSS) species allow organisms to detect and respond to metabolic and environmental stressors, such as exercise and altitude exposure. Whether redox markers and constituents of this ‘Reactive Species Interactome’ (RSI) differ in concentration between arterial and venous blood is unknown. We hypothesised that such measurements may provide useful insight into metabolic/redox regulation at the whole-body level and would be consistent between individuals exposed to identical challenges. An exploratory study was performed during the Xtreme Alps expedition in 2010 in which four healthy individuals (2 male, 2 female) underwent paired arterial and central venous blood sampling before, during and after performance of a constant-work-rate cardiopulmonary exercise test, at sea level and again at 4559 m. Unexpectedly, plasma total free thiol and free cysteine concentrations remained substantially elevated at altitude throughout exercise with minimal arteriovenous gradients. Free sulfide concentrations changed only modestly upon combined altitude/exercise stress, whereas bound sulfide levels were lower at altitude than sea-level. No consistent signal indicative of the expected increased oxidative stress and nitrate→nitrite→NO reduction was observed with 4-hydroxynonenal, isoprostanes, nitrate, nitrite, nitroso species and cylic guanosine monophosphate. However, the observed arteriovenous concentration differences revealed a dynamic pattern of response that was unique to each participant. This novel redox metabolomic approach of obtaining quantifiable ‘metabolic signatures’ to a defined physiological challenge could potentially offer new avenues for personalised medicine.
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2019 Cumpstey Redox Biol
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Pushing arterial-venous plasma
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More information
Accepted/In Press date: 14 January 2019
e-pub ahead of print date: 22 January 2019
Published date: 6 February 2019
Keywords:
Altitude, Hydrogen sulfide, Hypoxia, Oxidative stress, Oxygen, Thiols
Identifiers
Local EPrints ID: 428244
URI: http://eprints.soton.ac.uk/id/eprint/428244
ISSN: 2213-2317
PURE UUID: e5185b67-707a-4731-85e3-bdb2d04e445e
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Date deposited: 18 Feb 2019 17:30
Last modified: 24 Apr 2024 02:06
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Contributors
Author:
Andrew F. Cumpstey
Author:
Magdalena Minnion
Author:
Bernadette Fernandez
Author:
Monika Mikus-Lelinska
Author:
Kay Mitchell
Author:
Dan S. Martin
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