Abstract
The effects of spaceflight on human physiology is an increasingly studied field, yet the molecular mechanisms driving physiological changes remain unknown. With that in mind, this study was performed to obtain a deeper understanding of changes to the human proteome during space travel, by quantitating a panel of 125 proteins in the blood plasma of 18 Russian cosmonauts who had conducted long-duration missions to the International Space Station. The panel of labeled prototypic tryptic peptides from these proteins covered a concentration range of more than 5 orders of magnitude in human plasma. Quantitation was achieved by a well-established and highly-regarded targeted mass spectrometry approach involving multiple reaction monitoring in conjunction with stable isotope-labeled standards. Linear discriminant function analysis of the quantitative results revealed three distinct groups of proteins: 1) proteins with post-flight protein concentrations remaining stable, 2) proteins whose concentrations recovered slowly, or 3) proteins whose concentrations recovered rapidly to their pre-flight levels. Using a systems biology approach, nearly all of the reacting proteins could be linked to pathways that regulate the activities of proteases, natural immunity, lipid metabolism, coagulation cascades, or extracellular matrix metabolism.
Highlights
The effects of spaceflight on human physiology is an increasingly studied field, yet the molecular mechanisms driving physiological changes remain unknown
Because proteins are key players in the adaptive processes in an organism, a panoramic picture of changes in protein expression may provide information about the mechanisms of adaptation. In this mass spectrometry (MS)-based study, quantitative proteomic analysis was performed on 54 plasma samples collected from 18 cosmonauts before and after long-duration spaceflights on the Russian module of the International Space Station (ISS)
The 142 extracellular proteins targeted in this study were not selected for this particular space-oriented study but were a subset of proteins that were previously quantified in human plasma using multiple reaction monitoring (MRM)-MS with stable isotope-labeled peptides, and are reported to be putative biomarkers of non-communicable disease
Summary
Because proteins are key players in the adaptive processes in an organism, a panoramic picture of changes in protein expression may provide information about the mechanisms of adaptation In this mass spectrometry (MS)-based study, quantitative proteomic analysis was performed on 54 plasma samples collected from 18 cosmonauts before and after long-duration spaceflights on the Russian module of the International Space Station (ISS). The duration of these flights was 158 ± 15 days, with the exception of one cosmonaut who flew for 429 days. To the best of our knowledge, this study is the first relatively large-scale, MS-based proteomics investigation of the effects of space flight on plasma protein levels in cosmonauts’ blood, and it has yielded insights into the adaptive changes of this set of extracellular proteins
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