The effects of weightlessness on the human organism and mammalian cells

Current Molecular Medicine

Volumn 11, Issue 5, 2011, Pages 350-364

  Pietsch, J ^a,b   Bauer, J ^c   Egli, M ^d   Infanger, M ^e   Wise, P ^f   Ulbrich, C ^b   Grimm, D ^b,g  

^a FREIE UNIVERSITÄT BERLIN   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

^d ETH ZURICH   (Switzerland)

^e CENTRE HOSPITALIER DE LUXEMBOURG   (Luxembourg)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g AARHUS UNIVERSITY   (Denmark)

Author keywords

Apoptosis; Cells; Gravi sensitivity; Proteomics; Signal transduction; Space medicine; Weightlessness

Indexed keywords

ADAPTATION; AEROSPACE MEDICINE; APOPTOSIS; CELL ADHESION; CELL DIFFERENTIATION; CELL GROWTH; CELL MIGRATION; CELL PROLIFERATION; COSMONAUT; CYTOSKELETON; DEVICE; HEALTH STATUS; HEART DISEASE; HUMAN; HYDROSTATIC PRESSURE; IMMUNE SYSTEM; MACHINE; MAMMAL CELL; MICROGRAVITY; MUSCLE ATROPHY; NONHUMAN; OSTEOPOROSIS; RADIATION EXPOSURE; REVIEW; SIGNAL TRANSDUCTION; WEIGHTLESSNESS;

ADAPTATION, PHYSIOLOGICAL; AEROSPACE MEDICINE; ANIMALS; ASTRONAUTS; CYTOSKELETON; DISEASE; HUMANS; MUSCULAR ATROPHY; SPACE FLIGHT; WEIGHTLESSNESS; WEIGHTLESSNESS SIMULATION;

MAMMALIA;

EID: 79959313917     PISSN: 15665240     EISSN: 18755666     Source Type: Journal    
DOI: 10.2174/156652411795976600     Document Type: Review

References (147)

1. Haas U. In: Physik für Pharmazeuten und Mediziner; Stuttgart: Wiss Verl Ges 2002; Vol. 6: pp. 36-45.
2. Fong K. The limits of medicine - The next small step. BMJ 2004; 329: 1441-4.
3. White RJ, Averner M. Humans in space. Nature 2001; 409: 1115-8.
4. Planel H. Ed. Space and life (Boca Raton, London, New York, Washington DC, CEC Press), 2004.
5. Vernikos J. Human physiology in space. Bioessays 1996; 18: 1029-37.
6. Williams D, Kuipers A, Mukai C, et al. Acclimation during space flight: effects on human physiology. CMAJ 2009; 180: 1317-23.
7. Lipnicki DM, Gunga HC. Physical inactivity and cognitive functioning: results from bed rest studies. Eur J Appl Physiol 2009; 105: 27-35.
8. Adams GR, Caiozzo VJ, Baldwin KM. Skeletal muscle unweighting: spaceflight and ground-based models. J Appl Physiol 2003; 95: 2185-201.
9. Watenpaugh DE. Fluid volume control during short-term space flight and implications for human performance. J Exp Biol 2001; 204: 3209-15.
10. Lane HW, Feeback DL. Water and energy dietary requirements and endocrinology of human space flight. Nutrition 2002; 18: 820-8.
11. Buckey JC Jr, Lane LD, Levine BD, et al. Orthostatic intolerance after spaceflight. J Appl Physiol 1996; 81: 7-18.
12. Scott JM, Warburton DER, Williams D, et al. Challenges, concerns and problems: physiological consequences of spinal cord injury and microgravity. Spinal Cord 2011; 81: 7-18.
13. Fitts RH, Riley DR, Widrick JJ. Physiology of a microgravity environment invited review: microgravity and skeletal muscle. J Appl Physiol 2000; 89: 823-39.
14. LeBlanc AD, Spector ER, Evans HJ, et al. Skeletal responses to space flight and the bed rest analog: a review. J Musculoskelet Neuronal Interact 2007; 7: 33-47.
15. Trappe S, Costill D, Gallagher P, et al. Exercise in space: human skeletal muscle after 6 months aboard the International Space Station. J Appl Physiol 2009; 106: 1159-68.
16. Turner RT. Invited review: what do we know about the effects of spaceflight on bone? J Appl Physiol 2000; 89: 840-7.
17. Smith SM, Wastney ME, O'Brien KO, et al. Bone markers, calcium metabolism, and calcium kinetics during extendedduration space flight on the Mir space station. J Bone Miner Res 2005; 20: 208-18.
18. Shackelford LC, LeBlanc AD, Driscoll TB, et al. Resistance exercise as a countermeasure to disuse-induced bone loss. J Appl Physiol 2004; 97: 119-29.
19. Yoshimitsu K, Shiba N, Matsuse H, et al. Development of a training method for weightless environment using both electrical stimulation and voluntary muscle contraction. Tohoku J Exp Med 2010; 220: 83-93.
20. Merriman H, Jackson K. The effects of whole-body vibration training in aging adults: a systematic review. J Geriatr Phys Ther 2009; 32: 134-45.
21. LeBlanc AD, Driscol TB, Shackelford LC, et al. Alendronate as an effective countermeasure to disuse induced bone loss. J Musculoskelet Neuronal Interact 2002; 2: 335-43.
22. Jost PD. Simulating human space physiology with bed rest. Hippokratia 2008; 12: 37-40.
23. Cogoli A, Valluchi-Morf M, Bohringer HR, et al. Effect of gravity on lymphocyte proliferation. Life Sci Space Res 1979; 17: 219-24.
24. Gridley DS, Slater JM, Luo-Owen X, et al. Spaceflight effects on T lymphocyte distribution, function and gene expression. J Appl Physiol 2009; 106: 194-202.
25. Sonnenfeld G, Shearer WT. Immune function during space flight. Nutrition 2002; 18: 899-903.
26. Faller A, Schünke M, Schünke G. Der Körper des Menschen - Einführung in Bau und Funktion. George Thieme Verlag Stuttgart, Germany 1999.
27. Strollo F. Hormonal changes in humans during spaceflight. Adv Space Biol Med 1999; 7: 99-129.
28. Pierson DL, Stowe RP, Phillips TM, et al. Epstein-Barr virus shedding by astronauts during space flight. Brain Behav Immun 2005; 19: 235-42.
29. Bergquist J, Ohlsson B, Tarkowski A. Nuclear factor-kappa B is involved in the catecholaminergic suppression of immunocompetent cells. Ann N Y Acad Sci 2000; 917: 281-9.
30. Seiffert K, Granstein RD. Neuroendocrine regulation of skin dendritic cells. Ann N Y Acad Sci 2006; 1088: 195-206.
31. Charmandari E, Tsigos C, Chrousos G. Endocrinology of the stress response. Ann Rev Physiol 2005; 67: 259-84.
32. Black PH. Stress and the inflammatory response: A review of neurogenic inflammation. Brain Behav Immun 2002; 16: 622-53.
33. Buckey JC. Space Physiology. Oxford University Press, 2006, ISBN 0-19-513725-6.
34. Shearer WT, Reuben JM, Mullington JM, et al. Soluble TNF- α receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. J Allergy Clin Immunol 2001; 107: 165-70.
35. Shearer WT, Lee BN, Cron SG, et al. Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of pro-inflammatory cytokine IFN-γ during isolation of the Antarctic winter. J Allergy Clin Immunol 2002; 109: 854-57.
36. Crucioan BE, Cubbage ML, Sams CF. Altered cytokine production by specific human peripheral blood cell subsets immediately following space flight. J Interferon Cytokine Res 2000; 20: 547-56.
37. Hellweg CE, Baumstark-Khan C. Getting ready for the manned mission to Mars: the astronauts' risk from space radiation. Naturwissenschaften 2007; 94: 517-26.
38. Report of the United Nations Scientific Committee on the Effects of Atomic Radiation to the General Assembly, reference available from: http://www.unscear.org/docs/reports/gareport.pdf
39. Ohnishi K, Ohnishi T. The biological effects of space radiation during long stays in space. Biol Sci Space 2004; 18: 201-5.
40. Ikenaga M, Yoshikawa I, Kojo M, et al. Mutations induced in Drosophila during space flight. Biol Sci Space 1997; 11: 346-50.
41. Ishizaki K, Nishizawa K, Kato T, et al. Genetic changes induced in human cells in Space Shuttle experiment (STS-95). Aviat Space Environ Med 2001; 72: 794-8.
42. Bauer J, Grimm D. In: Cell mechanochemistry. Biological systems and factors inducing mechanical stress, such as light, pressure and gravity; Monici M, van Loon J, Eds. Kerala: Transworld Research Network 2010; chapter 6.
43. Grimm D, Bauer J, Kossmehl P, et al. Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells. FASEB J 2002; 16: 604-6.
44. Cogoli A. The effect of hypogravity and hypergravity on cells of the immune system. J Leukoc Biol 1993; 54: 259-68.
45. European Space Agency - Human spaceflight users - platforms. Reference available from: http://www.spaceflight.esa.int/users/index.cfm?act=default.page&level=11&page=385
46. Deutsches Zentrum für Luft- und Raumfahrt Schulinformation Raumfahrt - Raumfahrtmedizin 2001. Reference available from: http://www.dlr.de/desktopdefault.aspx/tabid-4741/7888_read-12417/
47. Schwarzenberg M, Pippia P, Meloni MA, et al. Signal transduction in T lymphocytes - A comparison of the data from space, the free fall machine and the random positioning machine. Adv Space Res 1999; 24: 793-800.
48. Sytkowski AJ, Davis, KL. Erythroid cell growth and differentiation in vitro in the simulated microgravity environment of the NASA rotating wall vessel bioreactor. In vitro Cell Dev Biol Anim 2001; 37: 79-83.
49. Grimm D, Bauer J, Infanger M, et al. The use of the random positioning machine for the study of gravitational effects on signal transduction in mammalian cells. Signal Transduction 2006; 6: 388-96.
50. Fitzgerald W, Chen S, Walz C, et al. Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station. In vitro Cell Dev Biol-Animal 2009; 45: 622-32.
51. Yi ZC, Xia B, Xue M, Zhang GY, et al. Simulated microgravity inhibits the proliferation of K562 erythroleukemia cells but does not result in apoptosis. Adv Space Res 2009; 44: 233-44.
52. Moes MJA, Gielen JC, Bleichrodt RJ, et al. Simulation of microgravity by magnetic levitation and random positioning: Effect on human A431 cell morphology. Microgravity Sci Technol 2011; 23: 249-61.
53. Mesland DAM. Novel ground-based facilities for research in the effects of weight. ESA Microgravity News 1996; 9: 5-10.
54. van Loon JJWA, Veldhuijzen JP, Kiss J, et al. Microgravity research starts on the ground! Apparatus for longterm ground-based hypo- and hypergravity studies. In: Utilization of the International Space Station, Proceedings of 2nd European Symposium, ESTEC, Noordwijk, The Netherlands, November 16-18, 1998; Wilson A, Paris: European Space Agency (ESA), ESA-SP 1999; 433: 415-19.
55. Mesland DA, Anton AH, Willemsen H, et al. The free fall machine - a ground-based facility for microgravity research in life sciences. Microgravity Sci Technol 1996; 9: 10-4.
56. Skagen EB, Inversen TH. Effect of simulated and real weightlessness on early regeneration stages of Brassica napus protoplasts. In vitro Cell Dev Biol-Plant 2000; 36: 312-8.
57. Wolf DA, Schwarz RP. Analysis of gravity-induced particle motion and fluid perfusion in the NASA-designed rotating zero-head-space tissue culture vessel. NASA Technical Paper 1991; 3143: 1-12.
58. Goodwin TJ, Prewett TL, Wolf DA, et al. Reduced shear stress: a major component in the ability of mammalian tissues to form three-dimensional assemblies in simulated microgravity. J Cell Biochem 1993; 51: 301-11.
59. Hammond TG, Benes E, O'Reilly KC, et al. Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle. Physiol Genomics 2000; 3: 163-73.
60. Hammond TG, Hammond JM. Optimized suspension culture: the rotating-wall vessel. Am J Physiol Renal Physiol 2001; 281, F12-25.
61. Wolf DA, Schwarz RP. Experimental measurement of the orbital paths of particles sedimenting within a rotating viscous fluid as influenced by gravity. NASA Technical Paper 1992; 3200: 1-15.
62. Briegleb W. Some qualitative and quantitative aspects of the fast-rotating clinostat as a research tool. AGSB Bull 1992; 5: 23-30.
63. Dedolph RR, Dipert MH. The physical basis of gravity stimulus nullification by clinostat rotation. Plant Physiol 1971; 47: 756-64.
64. Hoson T, Kamisaka S, Masuda Y, et al. Changes in plant growth processes under microgravity conditions simulated by a three-dimensional clinostat. Bot Mag 1992; 105: 53-70.
65. Hoson T, Kamisaka S, Masuda Y, et al. Evaluation of the three-dimensional clinostat as a simulator of weightlessness. Planta 1997; 203: S187-97.
66. Huijser RH. Desktop RPM: New small size microgravity simulator for the bioscience laboratory 2000. Reference available from: http://www.desc.med.vu.nl
67. European Space Agency - Astronauts - Human spaceflight and exploration - Christer Fuglesang's newsletter - My mission in Space. Reference available from: http://www.esa.int/esaHS/SEMRGYOFHTE_astronauts_0.html
68. Morbidelli L, Marziliano N, Basile V, et al. Effect of hypergravity on endothelial cell function and gene expression. Microgravity Sci Technol 2009; 21: 135-40.
69. Okaichi K, Ide M, Usui A, et al. Hypergravity induces phosphorylation of p53 at serine 15, but not an expression of p53-downstream genes. J Radiat Res 2004; 45: 399-403.
70. Holley DC, DeRoshia CW, Moran MM, et al. Chronic centrifugation (hypergravity) disrupts the circadian system of the rat. J Appl Physiol 2003; 95: 1266-78.
71. Matia I, Gonzales-Gamacho F, Herranz R, et al. Plant cell proliferation and growth are altered by microgravity conditions in spaceflight. J Plant Physiol 2010; 167: 184-93.
72. Cogoli A, Tschopp A, Fuchs-Bislin P. Cell sensitivity to gravity. Science 1984; 225: 228-30.
73. Rykova MP, Antropova EN, Larina, IM, Morukov BV. Humoral and cellular immunity in cosmonauts after the ISS missions. Acta Astronaut 2008; 63: 697-705.
74. Crucian BE, Stowe RP, Pierson DL, Sams CF. Immune system dysregulation following short- vs long-duration spaceflight. Aviat Space Environment Med 2008, 79: 835-43.
75. Cogoli A, Tschopp A. Lymphocyte reactivity during spaceflight. Immunol Today 1985; 6: 1-4.
76. Cogoli-Greuter M, Lovis P, Vadrucci S. Signal transduction in T cells: an overview. J Gravit Physiol 2004; 11: 53-6.
77. Cogoli-Greuter M, Spano A, Sciola L, et al. Influence of microgravity on mitogen binding, motility and cytoskeleton patterns of T lymphocytes and Jurkat cells. Experiments on sounding rockets. J Aerospace Env Med 1998; 35: 27-39.
78. Cogoli-Greuter M, Cogoli A, Spano A, et al. Influence of microgravity on mitogen binding and cytoskeleton in Jurkat cells: experiment on MAXUS-2. Proceedings 13th ESA Symposium on European Rocket and Balloon Programmes and related Research ESA 1997; SP-397, 73-76.
79. Boonyaratanakornkit J B, Cogoli A, Li CF, et al. Key gravitysensitive signaling pathways drive T cell activation. FASEB J 2005; 19: 2020-2.
80. Ullrich O, Thiel C, Zipp F, et al. Gravitationsbiologie. Zellen des Immunsystems und Schwerelosigkeit. BIOspektrum 2007; 4: 373-4.
81. Lewis ML. The cytoskeleton, apoptosis, and gene expression in T lymphocytes and other mammalian cells exposed to altered gravity. Adv Space Biol Med 2002; 8: 77-128.
82. Lewis ML, Reynolds JL, Cubano LA, et al. Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat). FASEB J 1998; 12: 1007-18.
83. Maccarrone M, Battista N, Meloni M, et al. Creating conditions similar to those that occur during exposure of cells to microgravity induces apoptosis in human lymphocytes by 5-lipoxygenase-mediated mitochondrial uncoupling and cytochrome c release. J Leukoc Biol 2003; 73: 472-81.
84. Hatton JP, Gaubert F, Cazenave JP, et al. Microgravity modifies protein kinase C isoform translocation in the human monocytic cell line U937 and human peripheral blood T-cells. J Cell Biochem 2002; 87: 39-50.
85. Ullrich O, Huber K, Lang K. Signal transduction in cells of the immune system in microgravity. Cell Commun Signal 2008; 6: 9.
86. Cogoli A, Gmünder FK. Effect of spaceflight on lymphocyte function and immunity. Supplement 14: Handbook of Physiology, Environmental Physiology Published Online: January 2011.
87. Hymer WC, Salada T, Cenci R, et al. Bioprocessing in microgravity: Applications of continuous flow electrophoresis to rat anterior pituitary particles. J Biotechnol 1996; 47: 353-65
88. Slivinsky GG, Hymer WC, Bauer J, Morrison DR. Cellular electrophoretic mobility data: A first approach to a database. Electrophoresis 1997; 18: 1109-19.
89. Schneider S, Askew CD, Brummer V, et al. The effect of parabolic flight on perceived physical, motivational and psychological state in men and women: Correlation with neuroendocrine stress parameters and electrocortical activity. Stress-Int J Biol Stress 2009; 12: 336-49.
90. Palermo-Neto J, Massoco CD, de Souza WR. Effects of physical and psychological stressors on behavior, macrophage activity, and Ehrlich tumor growth. Brain Behav Immun 2003; 17: 43-54.
91. Capulli M, Rufo A, Teti A, et al. Global transcriptome analysis in mouse calvarial osteoblasts highlights sets of genes regulated by modeled microgravity and identifies a mechanoresponsive osteoblast gene signature. J Cell Biochem 2009; 107: 240-52.
92. Patel MJ, Liu W, Sykes MC, et al. Identification of mechanosensitive genes in osteoblasts by comparative microarray studies using the rotating wall vessel and the random positioning machine. J Cell Biochem 2007; 101: 587-99.
93. Xing W, Baylink D, Kesavan C, et al. Global gene expression analysis in the bones reveals involvement of several novel genes and pathways in mediating an anabolic response of mechanical loading in mice. J Cell Biochem 2005; 6: 1049-60.
94. Saxena R, Pan G, McDonald JM. Osteoblast and osteoclast differentiation in modeled microgravity. Ann N Y Acad Sci 2007; 1116: 494-8.
95. Saxena R, Pan G, Dohm ED, et al. Modeled microgravity and hindlimb unloading sensitize osteoclast precursors to RANKL-mediated osteoclastogenesis. J Bone Miner Metab 2011; 29: 111-22.
96. Ko YJ, Zaharias RS, Seabold DA, et al. Osteoblast differentiation is enhanced in rotary cell culture simulated microgravity environments. J Prosthodont 2007; 16: 431-8.
97. Makihira S, Kawahara Y, Yuge L, et al. Impact of the microgravity environment in a 3- dimensional clinostat on osteoblast- and osteoclast-like cells. Cell Biol Int 2008; 32: 1176-81.
98. Hughes-Fulford M, Rodenacker K, Jütting U. Reduction of anabolic signals and alteration of osteoblast nuclear morphology in microgravity. J Cell Biochem 2006; 99: 435-49.
99. Hughes-Fulford M, Lewis ML. Effects of microgravity on osteoblast growth activation. Exp Cell Res 1996; 224: 103-9.
100. M. Signal transduction and mechanical stress. Sci STKE 2004; 249: RE12.
101. Cancedda R, Muraglia A. Osteogenesis in altered gravity. Cell Biology and Biotechnology in Space 2002; 8: 159-76.
102. Carmeliet G, Vico L, Bouillon R. Space flight: a challenge for normal bone homeostasis. Crit Rev Eukaryot Gene Expr 2001; 11: 131-44.
103. Vico L, Alexandre C. Microgravity and bone adaptation at the tissue level. J Bone Miner Res 1992; 7: 445-7.
104. Tamma R, Colaianni G, Camerino C, et al. Microgravity during spaceflight directly affects in vitro osteoclastogenesis and bone resorption. FASEB J 2009; 23: 549-54.
105. Monici M, Fusi F, Paglierani M, et al. Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells. J Cell Biochem 2006; 98: 65-80.
106. Freed LE, Langer R, Martin I, et al. Tissue engineering of cartilage in space. Proc Natl Acad Sci USA 1997; 94: 13885-90.
107. Stamenković V, Keller G, Nesic D, et al. Neocartilage formation in 1 g, simulated, and microgravity environments: implications for tissue engineering. Tissue Eng Part A 2010; 16: 1729-36.
108. Ulbrich C, Westphal K, Pietsch J, et al. Characterization of human chondrocytes exposed to simulated microgravity. Cell Physiol Biochem 2010; 25: 551-60.
109. Infanger M, Kossmehl P, Shakibaei M, et al. Induction of three-dimensional assembly and increase in apoptosis of human endothelial cells by simulated microgravity: Impact of vascular endothelial growth factor. Apoptosis 2006; 11: 749-64.
110. Grimm D, Infanger M, Westphal K, et al. A delayed type of three-dimensional growth of human endothelial cells under simulated weightlessness. Tissue Eng Part A 2009; 15: 2267-75.
111. Ulbrich C, Westphal K, Baatout S, et al. Effects of basic fibroblast growth factor on endothelial cells under conditions of simulated microgravity. J Cell Biochem 2008; 104: 1324-41.
112. Grimm D, Bauer J, Ulbrich C, et al. Different responsiveness of endothelial cells to vascular endothelial growth factor and basic fibroblast growth factor added to culture media under gravity and simulated microgravity. Tissue Eng Part A 2010; 16: 1559-73.
113. Infanger M, Ulbrich C, Baatout S, et al. Modeled gravitational unloading induced downregulation of endothelin-1 in human endothelial cells. J Cell Biochem 2007; 101: 1439-55.
114. Versari S, Villa A, Bradamante S, et al. Alterations of the actin cytoskeleton and increased nitric oxide synthesis are common features in human primary endothelial cell response to changes in gravity. Biochim Biophys Acta 2007; 1773: 1645-52.
115. Cotrupi S, Ranzani D, Maier JA. Impact of modeled microgravity on microvascular endothelial cells. Biochim Biophys Acta 2005; 1746. 163-8.
116. Carlsson SI, Bertilaccio MT, Ascari I, et al. Modulation of human endothelial cell behaviour in simulated microgravity. J Gravit Physiol 2002; 9: 273-4.
117. Buravkova LB, Romanov YA. The role of cytoskeleton in cell changes under condition of simulated microgravity. Acta Astronaut 2001; 48: 647-50.
118. Griffoni C, Di Molfetta S, Fantozzi L, et al. Modification of proteins secreted by endothelial cells during modeled low gravity exposure. J Cell Biochem 2011; 112: 265-72.
119. Kang CY, Zou L, Xuan M, et al. Impact of simulated microgravity on microvascular endothelial cell apoptosis. Eur J Appl Physiol 2011;[Epub ahead of print]
120. Grimm D, Kossmehl P, Shakibaei M, et al. Effects of simulated microgravity on thyroid carcinoma cells. J Gravit Physiol 2002; 9: 253-6.
121. Infanger M, Kossmehl P, Shakibaei M, et al. Long-term conditions of mimicked weightlessness influence the cytoskeleton in thyroid cells. J Gravit Physiol 2004; 11: 169-72.
122. Vassy J, Portet S, Beil M, et al. The effect of weightlessness on cytoskeleton architecture and proliferation of human breast cancer cell line MCF-7. FASEB J 2001; 15: 1104-6.
123. Qian A, Zhang W, Xie L, et al. Simulated weightlessness alters biological characteristics of human breast cancer cell line MCF-7. Acta Astronaut 2008; 63: 947-58.
124. Taga M, Yamauchi K, Odle J, et al. Melanoma growth and tumorigenicity in models of microgravity. Aviat Space Environ Med 2006; 77: 1113-6.
125. Ivanova K, Eiermann P, Tsiockas W, et al. Natriuretic peptide-sensitive guanylyl cyclase expression is downregulated in human melanoma cells at simulated weightlessness. Acta Astronaut 2011; 68: 652-5.
126. Grimm D, Wise P, Lebert M, et al. How and why does the proteome respond to microgravity? Expert Rev Proteomics 2011; 8: 13-27.
127. Uva BM, Masini MA, Sturla M, et al. Clinorotation-induced weightlessness influences the cytoskeleton of glial cells in culture. Brain Res 2002; 934: 132-9.
128. Uva BM, Masini MA, Sturla M, et al. Microgravity-induced apoptosis in cultured glial cells. Eur J Histochem 2002; 46: 209-14.
129. Rösner H, Wassermann T, Möller W, et al. Effects of altered gravity on the actin and microtubule cytoskeleton of human SH-SY5Y neuroblastoma cells. Protoplasma 2006; 229: 225-34.
130. Ingber D. How cells (might) sense microgravity. FASEB J 1999; 13: 3-15.
131. Kaneko T, Sasaki S, Umemoto Y, et al. Simulated conditions of microgravity increases progesterone production in I-10 cells of Leydig tumor cell line. Int J Urol 2008; 15: 245-50.
132. Marrero B, Messina JL, Heller R. Generation of a tumor spheroid in a microgravity environment as a 3D model of melanoma. In vitro Cell Dev Biol Anim 2009; 45: 523-34.
133. Ingram M, Techy GB, Saroufeem R, et al. Three-dimensional growth patterns of various human tumor cell lines in simulated microgravity of a NASA bioreactor. In vitro Cell Dev Biol Anim 1997; 33: 459-66.
134. Becker JL, Prewett TL, Spaulding GF, et al. Threedimensional growth and differentiation of ovarian tumor cell line in high aspect rotating-wall vessel: morphologic and embryologic considerations. J Cell Biochem 1993; 51: 283-9.
135. Becker JL. Women's health issues and space-based medical technologies. Earth Space Rev 1994; 3: 15-19.
136. Hammond DK, Becker J, Elliott TF, et al. Antigenic protein in microgravity-grown human mixed Mullerian ovarian tumor (LN1) cells preserved in RNA stabilizing agent. Gravit Space Biol Bull 2005; 18: 99-100.
137. Ingram M, Techy G, Ward B, et al. Tissue engineered tumor models. Biotech Histochem 2010; 85: 213-29.
138. Lewis ML, Cubano LA, Zhao B, et al. cDNA microarray reveals altered cytoskeletal gene expression in space-flown leukemic T-lymphocytes (Jurkat). FASEB J 2001; 15: 1783-5.
139. Pardo SJ, Patel MJ, Sykes MC, et al. Simulated microgravity using the Random Positioning Machine inhibits differentiation and alters gene expression profiles of 2T3 preosteoblasts. Am J Physiol - Cell Physiol 2005; 288: 1211-21.
140. Kumei Y, Morita S, Nakamura H, et al. Does microgravity induce apoptotic signal in rat osteoblasts via CJUN-Nterminal kinase? ESA Special Publications 2002; 501: 259-60.
141. Grun B, Benjamin E, Sinclair J, et al. Three-dimensional in vitro cell biology models of ovarian and endometrial cancer. Cell Prolif 2009; 42: 219-28.
142. Risso A, Tell G, Vascotto C, et al. Activation of human T lymphocytes under conditions similar to those that occur during exposure to microgravity: A proteomics study. Proteomics 2005; 5: 1827-37.
143. Schatten H, Lewis ML, Chakrabarti A. Spaceflight and clinorotation cause cytoskeleton and mitochondria changes and increase in apoptosis in cultured cells. Acta Astronaut 2001; 49: 399-418.
144. Obermaier C, Jankowski V, Schmutzler C, et al. Free-flow isoelectric focusing of proteins remaining in cell fragments following sonication of thyroid carcinoma cells. Electrophoresis 2005; 26: 2109-16.
145. Weber G, Bauer J. Counterbalancing hydrodynamic sample distortion effects increases resolution of free-flow zone electrophoresis. Electrophoresis 1998; 19: 1104-9
146. Pietsch J, Bauer J, Weber G, et al. Proteome analysis of thyroid cancer cells after long-term exposure to simulated microgravity. Microgravity Sci Technol 2011; on line published, DOI 10.1007/s12217-011-9258-5.
147. Pietsch J, Kussian R, Sickmann A, et al. Application of freeflow isoelectric focusing to identify protein candidates changing under microgravity conditions. Proteomics 2010; 10: 904-13.