Spaceflight induced changes in the human proteome

ABSTRACT Introduction: Spaceflight is one of the most extreme conditions encountered by humans: Individuals are exposed to radiation, microgravity, hypodynamia, and will experience isolation. A better understanding of the molecular processes induced by these factors may allow us to develop personalized countermeasures to minimize risks to astronauts. Areas covered: This review is a summary of literature searches from PubMed, NASA, Roskosmos and the authors’ research experiences and opinions. The review covers the available proteomic data on the effects of spaceflight factors on the human body, including both real space missions and ground-based model experiments. Expert commentary: Overall, the authors believe that the present background, methodology and equipment improvements will enhance spaceflight safety and support accumulation of new knowledge on how organisms adapt to extreme conditions.

[1]  S D Varfolomeev,et al.  [Proteomic analysis of exhaled breath condensate for diagnosis of pathologies of the respiratory system]. , 2015, Biomeditsinskaia khimiia.

[2]  Julian L. Griffin,et al.  Whole Blood Transcriptomics and Urinary Metabolomics to Define Adaptive Biochemical Pathways of High-Intensity Exercise in 50-60 Year Old Masters Athletes , 2014, PloS one.

[3]  Vladimir A. Ivanisenko,et al.  Permanent proteins in the urine of healthy humans during the Mars-500 experiment , 2015, J. Bioinform. Comput. Biol..

[4]  Masahiro Terada,et al.  Biomedical analysis of rat body hair after hindlimb suspension for 14 days , 2012 .

[5]  Victor A Convertino,et al.  Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures. , 2002, Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology.

[6]  P. J. Barnes,et al.  Exhaled breath condensate: methodological recommendations and unresolved questions , 2005, European Respiratory Journal.

[7]  R. Aisina,et al.  Structure and function of plasminogen/plasmin system , 2014, Russian Journal of Bioorganic Chemistry.

[8]  Fomin An.  Changes in the external respiratory indices of flight personnel as affected by helicopter flight , 1981 .

[9]  N. Prabhakar,et al.  Post-translational modification of proteins during intermittent hypoxia , 2008, Respiratory Physiology & Neurobiology.

[10]  Dieter Felsenberg,et al.  Disuse deterioration of human skeletal muscle challenged by resistive exercise superimposed with vibration: evidence from structural and proteomic analysis , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  Kriss Westphal,et al.  Characterization of Human Chondrocytes Exposed to Simulated Microgravity , 2010, Cellular Physiology and Biochemistry.

[12]  A R Kotovskaia,et al.  [Prediction of human orthostatic tolerance by changes in arterial and venous hemodynamics in the microgravity environment]. , 2013, Fiziologiia cheloveka.

[13]  A S Ushakov,et al.  Metabolic and hormonal status of crewmembers in short-term spaceflights. , 1987, Aviation, space, and environmental medicine.

[14]  D A Schoeller,et al.  Comparison of ground-based and space flight energy expenditure and water turnover in middle-aged healthy male US astronauts. , 1997, The American journal of clinical nutrition.

[15]  Hiroshi Yasuda,et al.  High Toxic Metal Levels in Scalp Hair of Infants and Children , 2005 .

[16]  Krista Vandenborne,et al.  Transcriptional pathways associated with skeletal muscle disuse atrophy in humans. , 2007, Physiological genomics.

[17]  R. Francavilla,et al.  Exhaled breath condensate cytokines and pH in pediatric asthma and atopic dermatitis. , 2008, Allergy and asthma proceedings.

[18]  Fabiola Olivieri,et al.  “Inflammaging” as a Druggable Target: A Senescence-Associated Secretory Phenotype—Centered View of Type 2 Diabetes , 2016, Oxidative medicine and cellular longevity.

[19]  G. Semenza,et al.  HIF-1-dependent respiratory, cardiovascular, and redox responses to chronic intermittent hypoxia. , 2007, Antioxidants & redox signaling.

[20]  V. A. Ivanisenko,et al.  The Proteome of a Healthy Human during Physical Activity under Extreme Conditions , 2014, Acta naturae.

[21]  A. Moser,et al.  Dyslipidemia and Atherosclerosis Induced by Chronic Intermittent Hypoxia Are Attenuated by Deficiency of Stearoyl Coenzyme A Desaturase , 2008, Circulation research.

[22]  Martin Hauer-Jensen,et al.  Space radiation and cardiovascular disease risk. , 2015, World journal of cardiology.

[23]  E V Guseva,et al.  [Blood albumin-globulin makeup in the crew of the Saliut-3 orbital station]. , 1979, Kosmicheskaia biologiia i aviakosmicheskaia meditsina.

[24]  Anatoly I Grigoriev,et al.  Targeted Quantitative Screening of Chromosome 18 Encoded Proteome in Plasma Samples of Astronaut Candidates. , 2016, Journal of proteome research.

[25]  Gerald Sonnenfeld,et al.  Use of animal models for space flight physiology studies, with special focus on the immune system. , 2005, Gravitational and space biology bulletin : publication of the American Society for Gravitational and Space Biology.

[26]  V V Polyakov,et al.  The alteration of human sleep and circadian rhythms during spaceflight , 1997, Journal of sleep research.

[27]  Hannelore Daniel,et al.  2D-electrophoresis and multiplex immunoassay proteomic analysis of different body fluids and cellular components reveal known and novel markers for extended fasting , 2011, BMC Medical Genomics.

[28]  P Bie,et al.  Unexpected renal responses in space , 2000, The Lancet.

[29]  T P Stein,et al.  Excretion of IL-6 by astronauts during spaceflight. , 1994, The American journal of physiology.

[30]  A Cogoli,et al.  Cell sensitivity to gravity. , 1984, Science.

[31]  Clarence Sams,et al.  Immune system dysregulation during spaceflight: clinical risk for exploration‐class missions , 2009, Journal of leukocyte biology.

[32]  Jens Hauslage,et al.  Short‐term weightlessness produced by parabolic flight maneuvers altered gene expression patterns in human endothelial cells , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  V. Polotsky,et al.  Obstructive sleep apnea and dyslipidemia: implications for atherosclerosis , 2010, Current opinion in endocrinology, diabetes, and obesity.

[34]  P. S. Demenkov,et al.  Reconstruction of associative protein networks connected with processes of sodium exchange regulation and sodium deposition in healthy volunteers based on urine proteome analysis , 2012, Human Physiology.

[35]  Victoria A Castro,et al.  Changes in neutrophil functions in astronauts , 2004, Brain, Behavior, and Immunity.

[36]  Mary Helen Barcellos-Hoff,et al.  Concepts and challenges in cancer risk prediction for the space radiation environment. , 2015, Life sciences in space research.

[37]  I G Popov,et al.  [Blood amino acids in astronauts before and after a 211-day space flight]. , 1984, Kosmicheskaia biologiia i aviakosmicheskaia meditsina.

[38]  Marc Heppener,et al.  Spaceward ho! , 2008, EMBO reports.

[39]  Bogusław Buszewski,et al.  Human exhaled air analytics: biomarkers of diseases. , 2007, Biomedical chromatography : BMC.

[40]  Jianguo Li,et al.  Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia. , 2007, Journal of applied physiology.

[41]  Edda Klipp,et al.  A systems biology approach: modelling of Aquaporin-2 trafficking. , 2010, Genome informatics. International Conference on Genome Informatics.

[42]  T P Stein,et al.  Protein kinetics during and after long-duration spaceflight on MIR. , 1999, American journal of physiology. Endocrinology and metabolism.

[43]  P. Johnson,et al.  Hematology and immunology studies: the second manned Skylab mission. , 1976, Aviation, space, and environmental medicine.

[44]  Popov Ig,et al.  [Blood amino acids in astronauts before and after a 211-day space flight]. , 1984 .

[45]  Cheuk-Kwan Sun,et al.  Intermittent Hypoxia Induces Hyperlipidemia in Lean Mice , 2005, Circulation research.

[46]  Irina M. Larina,et al.  Changes of human serum proteome profile during 7-day “dry” immersion , 2011 .

[47]  I. M. Larina,et al.  Modification of the Urine Proteome in Healthy Human during 21-day Bed Rest , 2017, Human Physiology.

[48]  Lorraine Brennan,et al.  Six weeks of a polarized training-intensity distribution leads to greater physiological and performance adaptations than a threshold model in trained cyclists. , 2013, Journal of applied physiology.

[49]  Kriss Westphal,et al.  A delayed type of three-dimensional growth of human endothelial cells under simulated weightlessness. , 2009, Tissue engineering. Part A.

[50]  Masahiro Terada,et al.  Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station , 2016, PloS one.

[51]  Clarence Sams,et al.  Monocyte phenotype and cytokine production profiles are dysregulated by short-duration spaceflight. , 2011, Aviation, space, and environmental medicine.

[52]  E S Tomilovskaia.  [Experiment with 5-day dry immersion: objectives, content and structure of the investigations, methods]. , 2011, Aviakosmicheskaia i ekologicheskaia meditsina = Aerospace and environmental medicine.

[53]  David G. Watson,et al.  The Application of Metabolomic Profiling to the Effects of Physical Activity , 2015 .

[54]  Martina Heer,et al.  Short‐term bed rest impairs amino acid‐induced protein anabolism in humans , 2004, The Journal of physiology.

[55]  Amsha Nahid,et al.  (1)H-NMR analysis of the human urinary metabolome in response to an 18-month multi-component exercise program and calcium-vitamin-D3 supplementation in older men. , 2014, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[56]  V. B. Noskov.  Adaptation of the water-electrolyte metabolism to space flight and at its imitation , 2013, Human Physiology.

[57]  O N Larina.  Protein composition in human plasma after long-term orbital missions and in rodent plasma after spaceflights on biosatellites "Cosmos-1887" and "Cosmos-2044". , 1991, The Physiologist.

[58]  Cecilia Gelfi,et al.  Comparative proteomic profile of rat sciatic nerve and gastrocnemius muscle tissues in ageing by 2‐D DIGE , 2009, Proteomics.

[59]  É. Rosnet,et al.  A Longitudinal Assessment of Psychological Adaptation During a Winter-Over in Antarctica , 2005 .

[60]  Inessa B Kozlovskaya,et al.  Russian system of countermeasures on board of the International Space Station (ISS): the first results. , 2004, Acta astronautica.

[61]  Blandine Comte,et al.  Mass spectrometry-based metabolomics for the discovery of biomarkers of fruit and vegetable intake: citrus fruit as a case study. , 2013, Journal of proteome research.

[62]  Anatoly I. Grigoriev,et al.  Changes in urine protein composition in human organism during long term space flights , 2012 .

[63]  Guseva Ev,et al.  [Blood albumin-globulin makeup in the crew of the Saliut-3 orbital station]. , 1979 .

[64]  C. Mukai,et al.  Acclimation during space flight: effects on human physiology , 2009, Canadian Medical Association Journal.

[65]  Bruno Domon,et al.  Longitudinal Urinary Protein Variability in Participants of the Space Flight Simulation Program. , 2016, Journal of proteome research.

[66]  Hans Binder,et al.  Time-course human urine proteomics in space-flight simulation experiments , 2014, BMC Genomics.

[67]  Thomas J. Goodwin,et al.  Personalized medicine in human space flight: using Omics based analyses to develop individualized countermeasures that enhance astronaut safety and performance , 2013, Metabolomics.

[68]  M. Raftery,et al.  Proteomics in detection and monitoring of asthma and smoking-related lung diseases , 2010, Expert review of proteomics.

[69]  Popova Ia,et al.  Metabolic and hormonal status of crewmembers in short-term spaceflights. , 1987 .

[70]  A N Fomin,et al.  [Blood fibrinogen during 7-day water immersion and short-term space flight]. , 1981, Kosmicheskaia biologiia i aviakosmicheskaia meditsina.

[71]  Roberto Guidetti,et al.  Space Flight Effects on Antioxidant Molecules in Dry Tardigrades: The TARDIKISS Experiment , 2015, BioMed research international.

[72]  R. Wolfe,et al.  Alterations in protein metabolism during space flight and inactivity. , 2002, Nutrition.

[73]  Steven M Day,et al.  Mortality among U.S. astronauts: 1980-2009. , 2010, Aviation, space, and environmental medicine.

[74]  Kenneth Watson,et al.  Stress proteins as biomarkers of oxidative stress: effects of antioxidant supplements. , 2000, Free radical biology & medicine.

[75]  Victoria A. Castro,et al.  Changes in monocyte functions of astronauts , 2005, Brain, Behavior, and Immunity.

[76]  E. Tomilovskaya,et al.  Long-term dry immersion: review and prospects , 2011, European Journal of Applied Physiology.

[77]  Tomilovskaia Es.  [Experiment with 5-day dry immersion: objectives, content and structure of the investigations, methods]. , 2011 .

[78]  K. Ohlendieck,et al.  Proteomic DIGE analysis of the mitochondria‐enriched fraction from aged rat skeletal muscle , 2009, Proteomics.

[79]  T. Stein,et al.  Plasma protein synthesis after spaceflight. , 2006, Aviation, space, and environmental medicine.

[80]  Scott M Smith,et al.  Plasma cytokine concentrations indicate that in vivo hormonal regulation of immunity is altered during long-duration spaceflight. , 2014, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[81]  Larina On.  Protein composition in human plasma after long-term orbital missions and in rodent plasma after spaceflights on biosatellites "Cosmos-1887" and "Cosmos-2044". , 1991 .

[82]  V B Noskov.  [Adaptation of water-electrolytes metabolism to space flight and in its imitation]. , 2013, Fiziologiia cheloveka.

[83]  Olof Beck,et al.  Potential of Mass Spectrometry in Developing Clinical Laboratory Biomarkers of Nonvolatiles in Exhaled Breath. , 2016, Clinical chemistry.

[84]  Dieter Felsenberg,et al.  Long term bed rest with and without vibration exercise countermeasures: Effects on human muscle protein dysregulation , 2010, Proteomics.

[85]  Ning Zhang,et al.  Proteomics and genomics of microgravity. , 2006, Physiological genomics.

[86]  Martina Heer,et al.  Life Sciences Research Standardization , 2007 .

[87]  I M Larina,et al.  [Identification proteins cardiovascular system in urine healthy subjects during "dry" immersion]. , 2014, Fiziologiia cheloveka.

[88]  Gabriela Kalna,et al.  A Study of the Effects of Exercise on the Urinary Metabolome Using Normalisation to Individual Metabolic Output , 2015, Metabolites.

[89]  Vladimir A Ivanisenko,et al.  Detection of renal and urinary tract proteins before and after spaceflight. , 2013, Aviation, space, and environmental medicine.

[90]  N. F. Samenkova,et al.  The Study of the Proteome of Healthy Human Blood Plasma under Conditions of Long-Term Confinement in an Isolation Chamber , 2013, Bulletin of Experimental Biology and Medicine.

[91]  W. Boron,et al.  The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters. , 2013, Physiological reviews.

[92]  Tetsuo Fukunaga,et al.  Ubiquitin ligase gene expression in healthy volunteers with 20‐day bedrest , 2006, Muscle & nerve.

[93]  Yosef Gruenbaum,et al.  High CO2 Leads to Na,K-ATPase Endocytosis via c-Jun Amino-Terminal Kinase-Induced LMO7b Phosphorylation , 2015, Molecular and Cellular Biology.

[94]  Marco V Narici,et al.  Muscles in microgravity: from fibres to human motion. , 2003, Journal of biomechanics.

[95]  G. Schulze-Tanzil,et al.  Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[96]  K. Node,et al.  Noninvasive method for assessing the human circadian clock using hair follicle cells , 2010, Proceedings of the National Academy of Sciences.

[97]  Wa Cao,et al.  Serum Levels of the Cancer-Testis Antigen POTEE and Its Clinical Significance in Non-Small-Cell Lung Cancer , 2015, PloS one.

[98]  I. M. Vikhlyantsev,et al.  Changes in isoform composition, structure, and functional properties of titin from mongolian gerbil (Meriones unguiculatus) cardiac muscle after space flight , 2011, Biochemistry (Moscow).

[99]  G. Semenza,et al.  Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1alpha. , 2006, Physiological genomics.

[100]  M. G. Wheatcroft,et al.  Clinical and Materials Sciences The Effect of Skylab on the Chemical Composition of Saliva , 1977, Journal of dental research.

[101]  Michael A. Gray,et al.  Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid secretion in airway epithelia , 2015, The Journal of physiology.

[102]  Akira Yasutake,et al.  Current hair mercury levels in Japanese: survey in five districts. , 2003, The Tohoku journal of experimental medicine.

[103]  G. Semenza,et al.  Regulation of physiological responses to continuous and intermittent hypoxia by hypoxia‐inducible factor 1 , 2006, Experimental physiology.

[104]  Gabriella Tedeschi,et al.  Protein pattern of Xenopus laevis embryos grown in simulated microgravity , 2011, Cell biology international.

[105]  A. R. Kotovskaya,et al.  Prediction of human orthostatic tolerance by changes in arterial and venous hemodynamics in the microgravity environment , 2013, Human Physiology.

[106]  R. Harrison,et al.  Effects of microgravity on osteoclast bone resorption and osteoblast cytoskeletal organization and adhesion. , 2011, Bone.

[107]  Peter J. Espenshade,et al.  SREBP Pathway Responds to Sterols and Functions as an Oxygen Sensor in Fission Yeast , 2005, Cell.

[108]  G. I. Samarin,et al.  Direct proteome profiling of the blood serum in cosmonauts after long-term space missions , 2014, Human Physiology.

[109]  N. Boisseau,et al.  1H NMR-based metabolomics approach for exploring urinary metabolome modifications after acute and chronic physical exercise , 2010, Analytical and bioanalytical chemistry.

[110]  R. Hughson,et al.  Cardiovascular response to 4 hours of 6 degrees head-down tilt or of 30 degrees head-up tilt bed rest. , 1990, Aviation, space, and environmental medicine.

[111]  Ingo Ruczinski,et al.  Metabolomic profiling of urine: response to a randomised, controlled feeding study of select fruits and vegetables, and application to an observational study , 2013, British Journal of Nutrition.

[112]  L A Palinkas,et al.  Stages of Change in Mood and Behavior During a Winter in Antarctica , 2000, Environment and behavior.

[113]  Alexander Meigal,et al.  Interplanetary space flight compared with fetal/neonatal motor strategy: Theoretical and practical implications. , 2012, Pathophysiology : the official journal of the International Society for Pathophysiology.

[114]  Qi Yue,et al.  Calcium metabolism and cardiovascular function after spaceflight. , 2002, Journal of applied physiology.

[115]  R. Whalen,et al.  Musculoskeletal adaptation to mechanical forces on Earth and in space. , 1993, The Physiologist.

[116]  A I Grigoriev,et al.  General mechanisms of the effect of weightlessness on the human body. , 1992, Advances in space biology and medicine.

[117]  V. M. Baranov,et al.  Physiological analysis of the possible causes of hypoxemia under conditions of weightlessness , 2011, Human Physiology.

[118]  W. Wilfinger,et al.  Sustained microgravity reduces intrinsic wound healing and growth factor responses in the rat , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[119]  Min Xu,et al.  Simulated microgravity using the Random Positioning Machine inhibits differentiation and alters gene expression profiles of 2T3 preosteoblasts. , 2005, American journal of physiology. Cell physiology.

[120]  Steven M Day,et al.  Mortality among Soviet and Russian cosmonauts: 1960-2013. , 2014, Aviation, space, and environmental medicine.

[121]  Louis S Stodieck,et al.  Effects of spaceflight on murine skeletal muscle gene expression. , 2009, Journal of applied physiology.

[122]  Leila Kheirandish-Gozal,et al.  Two-dimensional differential in-gel electrophoresis proteomic approaches reveal urine candidate biomarkers in pediatric obstructive sleep apnea. , 2009, American journal of respiratory and critical care medicine.

[123]  Vladimir A. Ivanisenko,et al.  Detection of Renal Tissue and Urinary Tract Proteins in the Human Urine after Space Flight , 2013, PloS one.

[124]  Jörn Rittweger,et al.  Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model. , 2002, American journal of physiology. Renal physiology.

[125]  M. Narici,et al.  From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006) , 2007, European Journal of Applied Physiology.

[126]  R Paus,et al.  The biology of hair follicles. , 1999, The New England journal of medicine.

[127]  Marcello Imbriani,et al.  Microgravity-driven remodeling of the proteome reveals insights into molecular mechanisms and signal networks involved in response to the space flight environment. , 2016, Journal of proteomics.

[128]  Zee Upton,et al.  Urinary biomarkers of physical activity: candidates and clinical utility , 2014, Expert review of proteomics.

[129]  A. Leblanc,et al.  Skeletal responses to space flight and the bed rest analog: a review. , 2007, Journal of musculoskeletal & neuronal interactions.

[130]  Hiroshi Ohshima,et al.  Intravenous Pamidronate Prevents Femoral Bone Loss and Renal Stone Formation During 90‐Day Bed Rest , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[131]  T P Stein,et al.  Diet and nitrogen metabolism during spaceflight on the shuttle. , 1996, Journal of applied physiology.

[132]  E V Guseva,et al.  [Effect of flights of varying duration on the blood protein makeup of cosmonauts]. , 1980, Kosmicheskaia biologiia i aviakosmicheskaia meditsina.

[133]  T. P. Stein.  Weight, muscle and bone loss during space flight: another perspective , 2012, European Journal of Applied Physiology.

[134]  Michael Lebert,et al.  The impact of microgravity-based proteomics research , 2014, Expert review of proteomics.

[135]  Proto Pippia,et al.  Space flight affects motility and cytoskeletal structures in human monocyte cell line J‐111 , 2011, Cytoskeleton.

[136]  Alamelu Sundaresan,et al.  The Impact of Simulated and Real Microgravity on Bone Cells and Mesenchymal Stem Cells , 2014, BioMed research international.