Biological Effects of Space Radiation and Microgravity on Mammalian Cells (NeuroRad) - 09.17.14
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Biological Effects of Space Radiation and Microgravity on Mammalian Cells (NeuroRad) studies the effects of space radiation on the human neuroblastoma cell (nerve cell containing a tumor) line in microgravity.
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Space travel is rough on human cells. Studying human nerve cells with tumors, and changes in their genetic materials, show that short- and long-term cultures of these cells on the space station grow faster and generate more reactive oxygen species, along with increased heat shock proteins and antioxidant enzymes than those cultured on Earth, meaning that toxic stress occurs in the microgravity cells. Results could advance new treatments and preventative measures for the effects of radiation on humans in space and for related diseases and aging on Earth.
Sponsoring Space Agency
Japan Aerospace Exploration Agency (JAXA)
ISS Expedition Duration
March 2010 - September 2010
Previous ISS Missions
NeuroRad was first operated on ISS Expedition 19/20.
- NeuroRad will investigate the biological effects of space radiation on mammalian nerve cells using SK-N-SH (human neuroblastoma cell line).
- NeuroRad will evaluate the risk factors of long-term space flight by investigating the ability to recover from radiation damage aquired in microgravity. NeuroRad will also evaluate the effects of radiation accumulation as a result of long-term space flight missions.
- NeuroRad will focus on changes in the mitochondria-related gene expression, since the mitochondria is well known for having a crucial role in apotosis (programmed cell death).
- After recovery, the effects of radiation in microgravity will be comprehensively analyzed using the following techniques: nuclear DNA microaray, western blotting, and mutation assays.
Radiation effects are critical for biological creatures. The data collected during this investigation may lead a greater understanding of how the radiation defense system is affected by different factors from space radiation and microgravity environment. The data could be applied to develop new treatments and preventative measures for the effects of radiation, and to further investigate the effects of human long-duration stays in space.
Researchers investigated the transcription factors that regulate Cbl-b expression using rat L6 myoblasts and differentiated myotubes. The biological relevance of Cbl-b expression as a sensor of unloading is strengthened by the findings that both oxidative stress and 3-D-clinorotation induced Cbl-b expression in L6 myoblasts and myotubes. These findings suggest that increased levels of ROS link mechanical stress to downstream signaling pathways. In the present study, we observed that H2O2 treatment promoted the binding of Egr to the 5'-franking region of Cbl-b gene. Moreover, 3-D-clinorotation and H2O2 each induced the expression of Cbl-b in a manner accompanied by the early expression of Egrs 1-3. This is consistent with the findings of another laboratory using Egr-2 or Egr-3 knockout mice. The results obtained in Egr knockdown studies (siRNA) confirm that Egr transcription factors play a major role in 3-D-clinorotation-mediated Cbl-b induction. Together, these data uncover the molecular mechanism through which mechanical unloading is transduced into biochemical signaling in skeletal muscle. Several lines of evidence in diverse cell types point to the involvement of Egr transcription factors in the response to mechanical stress. Egr expression induced by 3-D-clinorotation occurs within 90 minutes of stimulation, indicating that the Egr genes are in close temporal proximity to the mechanical stress “receptor.” Consistent with the role of oxidants as the second messengers of Egr activation and downstream unloading responses, the ERK1/2 pathway, a common target of oxidative signaling, was activated by 3-D-clinorotation and H2O2. Together, these results are consistent with the findings of other laboratories; they showed that immobilization or tail suspension increased oxidative stress-dependent signaling in rat skeletal muscles. Recent studies have identified several signaling molecules, such as ASK1, that mediate oxidative stress-dependent activation of MAPK signaling. An important area for further investigation will be to identify the molecules that regulate ROS production in distinct cellular compartments (plasma membrane, mitochondria) in response to unloading. It is anticipated that these molecules may be the direct receptors/sensors for unloading stress. This hypothesis is supported by previous finding that the disrupted expression of cytoskeletal genes, especially mitochondria-anchoring protein genes, is associated with large imbalances in the expression of genes encoding diverse members of the electron transport system in the mitochondria of space-flown skeletal muscle.
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Indo HP, Davidson M, Yen H, Suenaga S, Tomita K, Nishii T, Higuchi M, Koga K, Ozawa T, Majima HJ. Evidence of ROS generation by mitochondria in cells with impaired electron transport chain and mitochondrial DNA damage. Mitochondrion. 2007 February; 7(1-2): 106-118. DOI: 10.1016/j.mito.2006.11.026. PMID: 17307400.
Indo HP, Nakanishi I, Ohkubo K, Yen H, Nyui M, Manda S, Matsumoto K, Fukuhara K, Anzai K, Ikota N, Matsui H, Minamiyama Y, Nakajima A, Ichikawa H, Fukuzumi S, Ozawa T, Mukai C, Majima HJ. Comparison of in vivo and in vitro antioxidative parameters for eleven food factors. RSC Advances. 2013; 3(14): 4535. DOI: 10.1039/c3ra22686g.
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