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.
Highlights
Redox reactions constitute one of the most fundamental integrative regulatory systems that support human physiology, and our understanding of these systems has evolved at a remarkable rate in recent years
One subject was initially unwell at 4559 m, developing symptoms of acute mountain sickness shortly after arrival at 4559 m, but these had fully resolved before commencing the exercise protocol
The results from our present study demonstrate that exposure to hypobaric hypoxia is accompanied by markedly higher concentrations of circulating cysteine and protein free thiols yet lower concentrations of sulfate and thiosulfate, with only moderate changes in other aminothiols and sulfide
Summary
Redox reactions constitute one of the most fundamental integrative regulatory systems that support human physiology, and our understanding of these systems has evolved at a remarkable rate in recent years. As well as controlling whole body metabolism, the chemical and functional interactions between these species (which we recently defined to constitute the ‘Reactive Species Interactome’; RSI [5]) allows organisms to sense and adapt to the many environmental stressors they experience throughout everyday life. We believe characterisation of these processes to be absolutely essential to arrive at a truly integrative understanding of human physiology in health and disease, it is not clear at the moment what exactly we should measure to gauge the functional status of this RSI and its key regulatory nodes
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