Protein expression changes caused by spaceflight as measured for 18 Russian cosmonauts

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.

Modulation of Iberian Ribbed Newt Complement Component C3 by Stressors Similar to those Encountered during a Stay Onboard the International Space Station

“…Furthermore, radiation upregulate C3a and C5a production [55] and modified membranes of late apoptotic and necrotic cells are potent activators of complement [33]. Thus, changes in coagulation cascade protein expression noted during and after spaceflight [29,71,72], space radiation, and apoptosis, which is frequently increased in microgravity [73,74,75,76], could increase the production of C3a and C5a. Since these molecules have pro-inflammatory properties and increase the expression of MHC (major histocompatibility complex) class II and costimulatory molecules on antigen presenting cells such as dendritic cells, they could influence T cell activation and polarization towards a tolerogenic or inflammatory profile [77,78].…”

The molecular mechanisms driving physiological changes after long duration space flights revealed by quantitative analysis of human blood proteins

“…All steps of solution and sample preparation, LC/MRM-MS parameters, are described in the article [ 3 ]. LC/MRM-MS analysis was performed with a Zorbax Eclipse Plus RP-UHPLC column on a 1290 Infinity UPLC system (all from Agilent Technologies) that was interfaced to a triple quadrupole mass spectrometer (Agilent 6490) via Agilent’s Jet Stream™ source, operated in the positive-ion ESI mode.…”

“…Proteomic methods with biological databases open new opportunities to reveal proteins participating in adaptive and pathological processes [ 2 ]. We have already analyzed the same set of cosmonauts’ blood proteins [ 3 ]. There were three distinct groups of proteins: 1) proteins with post-flight protein concentrations remaining stable; 2) proteins whose concentrations recovered slowly; and 3) proteins whose concentrations recovered rapidly to their pre-flight levels.…”

The thrombotic risk of spaceflight: has a serious problem been overlooked for more than half of a century?

“…14 Coagulation protein expression, in particular the fibrinogen beta chain, was changed in cosmonauts after long-term spaceflight but recovered within 1 week after return to Earth. 42 The majority of US female astronauts take oral contraceptives for cycle suppression during their space mission, which would double their risk of sustaining deep venous thrombosis on Earth. However, this risk calculation may not be simply transferable to their stay in space.…”