Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Beck,Michaël; Moreels,Marjan; Quintens,Roel; Abou-El-Ardat,Khalil; El-Saghire,Hussein; Tabury,Kevin; Michaux,Arlette; Janssen,Ann; Neefs,Mieke; Van Oostveldt,Patrick; De Vos,Winnok  H.; Baatout,Sarah

doi:10.3892/ijmm.2014.1785

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Authors:
- Michaël Beck
- Marjan Moreels
- Roel Quintens
- Khalil Abou-El-Ardat
- Hussein El-Saghire
- Kevin Tabury
- Arlette Michaux
- Ann Janssen
- Mieke Neefs
- Patrick Van Oostveldt
- Winnok H. De Vos
- Sarah Baatout
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Affiliations: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium, Department of Molecular Biotechnology, Ghent University, Ghent, Belgium
Published online on: May 22, 2014 https://doi.org/10.3892/ijmm.2014.1785
Pages: 606-615

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Abstract

Microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist to simulate space flight experiments. In the present study, an experimental model was utilized to monitor gene expression changes in fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation (IR), comprising a mixture of high‑linear energy transfer (LET) neutrons and low-LET gamma-rays, and/or simulated microgravity using the random positioning machine (RPM), after which microarrays were performed. The data were analyzed both by gene set enrichment analysis (GSEA) and single gene analysis (SGA). Simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes. Three of these genes are targets of the nuclear factor‑erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell response to simulated microgravity. In addition, simulated gravity decreased the expression of genes involved in cytoskeleton remodeling, which may have been caused by the downregulation of the serum response factor (SRF), possibly through the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the downregulation of genes involved in cytoskeleton remodeling, as well as in cell cycle regulation and DNA damage response pathways. Many of the genes or gene sets that were altered in the individual treatments (RPM or IR) were not altered in the combined treatment (RPM and IR), indicating a complex interaction between RPM and IR.

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1	Huijser RH: Desktop RPM: new small size microgravity simulator for the bioscience laboratory. Fokker Space FS-MG-R00-017. 1–5. 2000.
2	van Loon JJWA: Some history and use of the random positioning machine, RPM, in gravity related research. Adv Space Res. 39:1161–1165. 2007.
3	Borst A and van Loon J: Technology and developments for the random positioning machine, RPM. Microgravity Sci Technol. 21:287–292. 2009. View Article : Google Scholar
4	Kraft TF, van Loon JJ and Kiss JZ: Plastid position in arabidopsis columella cells is similar in microgravity and on a random-positioning machine. Planta. 211:415–422. 2000. View Article : Google Scholar : PubMed/NCBI
5	Villa A, Versari S, Maier JA and Bradamante S: Cell behavior in simulated microgravity: a comparison of results obtained with RWV and RPM. Gravit Space Biol Bull. 18:89–90. 2005.
6	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. 16:1559–1573. 2010. View Article : Google Scholar
7	Mastroleo F, Van Houdt R, Leroy B, et al: Experimental design and environmental parameters affect Rhodospirillum rubrum S1H response to space flight. ISME J. 3:1402–1419. 2009. View Article : Google Scholar : PubMed/NCBI
8	Shi J and Walker MG: Gene set enrichment analysis (GSEA) for interpreting gene expression profiles. Curr Bioinform. 2:133–137. 2007. View Article : Google Scholar
9	Subramanian A, Tamayo P, Mootha VK, et al: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI
10	El-Saghire H, Thierens H, Monsieurs P, Michaux A, Vandevoorde C and Baatout S: Gene set enrichment analysis highlights different gene expression profiles in whole blood samples X-irradiated with low and high doses. Int J Radiat Biol. 89:628–638. 2013. View Article : Google Scholar : PubMed/NCBI
11	Vanhavere F, Loos M, Plompen AJM, Wattecamps E and Thierens H: A combined use of the BD-PND and BDT bubble detectors in neutron dosimetry. Radiat Meas. 29:573–577. 1998. View Article : Google Scholar
12	Cucinotta FA, Kim MH, Willingham V and George KA: Physical and biological organ dosimetry analysis for international space station astronauts. Radiat Res. 170:127–138. 2008. View Article : Google Scholar : PubMed/NCBI
13	Crawford-Young SJ: Effects of microgravity on cell cytoskeleton and embryogenesis. Int J Dev Biol. 50:183–191. 2006. View Article : Google Scholar : PubMed/NCBI
14	Meloni MA, Galleri G, Pani G, Saba A, Pippia P and Cogoli-Greuter M: Space flight affects motility and cytoskeletal structures in human monocyte cell line J-111. Cytoskeleton (Hoboken). 68:125–137. 2011. View Article : Google Scholar : PubMed/NCBI
15	Hayes JD and McLellan LI: Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free Radic Res. 31:273–300. 1999. View Article : Google Scholar : PubMed/NCBI
16	Chen Y, Johansson E, Fan Y, et al: Early onset senescence occurs when fibroblasts lack the glutamate-cysteine ligase modifier subunit. Free Radic Biol Med. 47:410–418. 2009. View Article : Google Scholar : PubMed/NCBI
17	Haines DD, Lekli I, Teissier P, Bak I and Tosaki A: Role of haeme oxygenase-1 in resolution of oxidative stress-related pathologies: Focus on cardiovascular, lung, neurologic and kidney disorders. Acta Physiol (Oxf). 204:487–501. 2012. View Article : Google Scholar
18	Lee JC, Kinniry PA, Arguiri E, et al: Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice. Radiat Res. 173:590–601. 2010. View Article : Google Scholar : PubMed/NCBI
19	Hayes JD and McMahon M: NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci. 34:176–188. 2009. View Article : Google Scholar : PubMed/NCBI
20	Wang J, Zhang J, Bai S, et al: Simulated microgravity promotes cellular senescence via oxidant stress in rat PC12 cells. Neurochem Int. 55:710–716. 2009. View Article : Google Scholar : PubMed/NCBI
21	Nikawa T, Ishidoh K, Hirasaka K, et al: Skeletal muscle gene expression in space-flown rats. FASEB J. 18:522–524. 2004.PubMed/NCBI
22	Liu Y and Wang E: Transcriptional analysis of normal human fibroblast responses to microgravity stress. Genomics Proteomics Bioinformatics. 6:29–41. 2008. View Article : Google Scholar : PubMed/NCBI
23	Carson JA, Culberson DE, Thompson RW, Fillmore RA and Zimmer W: Smooth muscle gamma-actin promoter regulation by RhoA and serum response factor signaling. Biochim Biophys Acta. 1628:133–139. 2003. View Article : Google Scholar
24	Philippar U, Schratt G, Dieterich C, et al: The SRF target gene Fhl2 antagonizes RhoA/MAL-dependent activation of SRF. Mol Cell. 16:867–880. 2004. View Article : Google Scholar : PubMed/NCBI
25	Beamish JA, He P, Kottke-Marchant K and Marchant RE: Molecular regulation of contractile smooth muscle cell phenotype: implications for vascular tissue engineering. Tissue Eng Part B Rev. 16:467–491. 2010. View Article : Google Scholar : PubMed/NCBI
26	Olson EN and Nordheim A: Linking actin dynamics and gene transcription to drive cellular motile functions. Nat Rev Mol Cell Biol. 11:353–365. 2010. View Article : Google Scholar
27	Sun Q, Chen G, Streb JW, et al: Defining the mammalian CArGome. Genome Res. 16:197–207. 2006. View Article : Google Scholar : PubMed/NCBI
28	Ingber DE: Tensegrity II. How structural networks influence cellular information processing networks. J Cell Sci. 116:1397–1408. 2003. View Article : Google Scholar : PubMed/NCBI
29	Meloni MA, Galleri G, Pippia P and Cogoli-Greuter M: Cytoskeleton changes and impaired motility of monocytes at modelled low gravity. Protoplasma. 229:243–249. 2006. View Article : Google Scholar : PubMed/NCBI
30	Servotte S, Zhang Z, Lambert CA, et al: Establishment of stable human fibroblast cell lines constitutively expressing active rho-GTPases. Protoplasma. 229:215–220. 2006. View Article : Google Scholar
31	Nichols HL, Zhang N and Wen X: Proteomics and genomics of microgravity. Physiol Genomics. 26:163–171. 2006. View Article : Google Scholar : PubMed/NCBI
32	Loesberg WA, Walboomers XF, van Loon JJWA and Jansen JA: Simulated microgravity activates MAPK pathways in fibroblasts cultured on microgrooved surface topography. Cell Motil Cytoskeleton. 65:116–129. 2008. View Article : Google Scholar : PubMed/NCBI
33	Hall A: Rho GTPases and the control of cell behaviour. Biochem Soc Trans. 33:891–895. 2005. View Article : Google Scholar : PubMed/NCBI
34	Jeggo P: The role of the DNA damage response mechanisms after low-dose radiation exposure and a consideration of potentially sensitive individuals. Radiat Res. 174:825–832. 2010. View Article : Google Scholar : PubMed/NCBI
35	Jeggo P and Lavin MF: Cellular radiosensitivity: how much better do we understand it? Int J Radiat Biol. 85:1061–1081. 2009. View Article : Google Scholar : PubMed/NCBI
36	Grimm D, Wise P, Lebert M, Richter P and Baatout S: How and why does the proteome respond to microgravity? Expert Rev Proteomics. 8:13–27. 2011. View Article : Google Scholar : PubMed/NCBI
37	Gabryś, Greco O, Patel G, Prise KM, Tozer GM and Kanthou C: Radiation effects on the cytoskeleton of endothelial cells and endothelial monolayer permeability. Int J Radiat Oncol Biol Phys. 69:1553–1562. 2007.PubMed/NCBI
38	Rousseau M, Gaugler MH, Rodallec A, Bonnaud S, Paris F and Corre I: Rhoa GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration. Biochem Biophys Res Commun. 414:750–755. 2011. View Article : Google Scholar : PubMed/NCBI
39	Etienne-Manneville S and Hall A: Rho GTPases in cell biology. Nature. 420:629–635. 2002. View Article : Google Scholar