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Oxidative Stress and Damage in the Space Environment: Physiological Ground and Flight Parallels

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 July 2018) | Viewed by 54066

Special Issue Editors

1. Sovaris Aerospace, Research Innovation, Infectious Disease Research Center Colorado State University, Fort Collins, CO 80521, USA
2. The National Aeronautics and Space Administration (NASA Retired) Johnson Space Center, Houston, TX 77058, USA
Interests: ageing; oxidative stress and damage; antioxidants; radiation toxicity; inflammation; genomics; proteomics; metabolomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Technological advances now allow the planning of deep space exploration missions with the aim to discover new habitats for humankind. The National Aeronautics and Space Administration (NASA) has spearheaded this effort and the research into the identification of risks to crew members associated with such lengthy missions. Exciting work from a multitude of investigators across the US, Canada, Europe, and Japan have identified oxidative damage as a key risk factor to major organs and systems physiologies that could pose a threat to the health of the astronauts and the success of the mission. Through “Omics technologies” and other advanced analyses we now have defined methods to begin comparison of human physiological responses in space flight to ground based One Earth Normal (OEN) physiologies. This Special Issue of IJMS is dedicated to providing a comprehensive overview of the identified risks in space flight and habitation and will focus on ground based vs. flight comparisons of how oxidative stress when exposed to space-relevant conditions such as cosmic/galactic radiation, solar particle events, hypogravity (G-variations and partial gravity) and hypoxia/hyperoxia or any aggregate combination of stressors effects the human physiology. Much can be learned from examination and analyses of the parallel human physiology response and how it adapts to the hostile environment of space.

Prof. Dr. Melpo Christofidou-Solomidou
Dr. Thomas J. Goodwin
Guest Editors

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Keywords

  • Hypoxia/hyperoxia
  • Omics analyses
  • Cosmic/galactic radiation
  • Solar particles
  • Space travel
  • Mars habitation
  • Environmental stressors
  • Hypogravity/gravity variations
  • Oxidative stress

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Published Papers (10 papers)

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Research

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16 pages, 1834 KiB  
Article
Modulation of Iberian Ribbed Newt Complement Component C3 by Stressors Similar to those Encountered during a Stay Onboard the International Space Station
by Nathan Guéguinou, Jérémy Jeandel, Sandra Kaminski, Sarah Baatout, Stéphanie Ghislin and Jean-Pol Frippiat
Int. J. Mol. Sci. 2019, 20(7), 1579; https://doi.org/10.3390/ijms20071579 - 29 Mar 2019
Cited by 9 | Viewed by 3015
Abstract
The complement system plays an important role in inflammation, innate and acquired immunity, as well as homeostasis. Despite these functions, the effects of spaceflight conditions on the complement system have not yet been intensively studied. Consequently, we investigated the effects of five types [...] Read more.
The complement system plays an important role in inflammation, innate and acquired immunity, as well as homeostasis. Despite these functions, the effects of spaceflight conditions on the complement system have not yet been intensively studied. Consequently, we investigated the effects of five types of chronic stressors, similar to those encountered during a stay onboard the International Space Station, on C3 expression in larvae of the urodele amphibian Pleurodeles waltl. We focused on C3 because it is a critical component of this system. These studies were completed by the analysis of adult mice exposed to two models of inflight stressors. Our data show that simulating space radiation, or combining a modification of the circadian rhythm with simulated microgravity, affects the amount of C3 proteins. These results suggest that C3 expression could be modified under real spaceflight conditions, potentially increasing the risk of inflammation and associated tissue damage. Full article
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27 pages, 9151 KiB  
Article
LGM2605 Reduces Space Radiation-Induced NLRP3 Inflammasome Activation and Damage in In Vitro Lung Vascular Networks
by Shampa Chatterjee, Ralph A. Pietrofesa, Kyewon Park, Jian-Qin Tao, Alejandro Carabe-Fernandez, Abigail T. Berman, Constantinos Koumenis, Thais Sielecki and Melpo Christofidou-Solomidou
Int. J. Mol. Sci. 2019, 20(1), 176; https://doi.org/10.3390/ijms20010176 - 05 Jan 2019
Cited by 17 | Viewed by 5215
Abstract
Updated measurements of charged particle fluxes during the transit from Earth to Mars as well as on site measurements by Curiosity of Martian surface radiation fluxes identified potential health hazards associated with radiation exposure for human space missions. Designing mitigation strategies of radiation [...] Read more.
Updated measurements of charged particle fluxes during the transit from Earth to Mars as well as on site measurements by Curiosity of Martian surface radiation fluxes identified potential health hazards associated with radiation exposure for human space missions. Designing mitigation strategies of radiation risks to astronauts is critical. We investigated radiation-induced endothelial cell damage and its mitigation by LGM2605, a radioprotector with antioxidant and free radical scavenging properties. We used an in vitro model of lung vascular networks (flow-adapted endothelial cells; FAECs), exposed to gamma rays, low/higher linear energy transfer (LET) protons (3–4 or 8–10 keV/µm, respectively), and mixed field radiation sources (gamma and protons), given at mission-relevant doses (0.25 gray (Gy)–1 Gy). We evaluated endothelial inflammatory phenotype, NLRP3 inflammasome activation, and oxidative cell injury. LGM2605 (100 µM) was added 30 min post radiation exposure and gene expression changes evaluated 24 h later. Radiation induced a robust increase in mRNA levels of antioxidant enzymes post 0.25 Gy and 0.5 Gy gamma radiation, which was significantly decreased by LGM2605. Intercellular cell adhesion molecule-1 (ICAM-1) and NOD-like receptor protein 3 (NLRP3) induction by individual or mixed-field exposures were also significantly blunted by LGM2605. We conclude that LGM2605 is a likely candidate to reduce tissue damage from space-relevant radiation exposure. Full article
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16 pages, 257 KiB  
Article
Proteomic Analysis of Mouse Brain Subjected to Spaceflight
by Xiao Wen Mao, Lawrence B. Sandberg, Daila S. Gridley, E. Clifford Herrmann, Guangyu Zhang, Ravi Raghavan, Roman A. Zubarev, Bo Zhang, Louis S. Stodieck, Virginia L. Ferguson, Ted A. Bateman and Michael J. Pecaut
Int. J. Mol. Sci. 2019, 20(1), 7; https://doi.org/10.3390/ijms20010007 - 20 Dec 2018
Cited by 19 | Viewed by 5495
Abstract
There is evidence that spaceflight poses acute and late risks to the central nervous system. To explore possible mechanisms, the proteomic changes following spaceflight in mouse brain were characterized. Space Shuttle Atlantis (STS-135) was launched from the Kennedy Space Center (KSC) on a [...] Read more.
There is evidence that spaceflight poses acute and late risks to the central nervous system. To explore possible mechanisms, the proteomic changes following spaceflight in mouse brain were characterized. Space Shuttle Atlantis (STS-135) was launched from the Kennedy Space Center (KSC) on a 13-day mission. Within 3–5 h after landing, brain tissue was collected to evaluate protein expression profiles using quantitative proteomic analysis. Our results showed that there were 26 proteins that were significantly altered after spaceflight in the gray and/or white matter. While there was no overlap between the white and gray matter in terms of individual proteins, there was overlap in terms of function, synaptic plasticity, vesical activity, protein/organelle transport, and metabolism. Our data demonstrate that exposure to the spaceflight environment induces significant changes in protein expression related to neuronal structure and metabolic function. This might lead to a significant impact on brain structural and functional integrity that could affect the outcome of space missions. Full article
25 pages, 6264 KiB  
Article
Whole-Body 12C Irradiation Transiently Decreases Mouse Hippocampal Dentate Gyrus Proliferation and Immature Neuron Number, but Does Not Change New Neuron Survival Rate
by Giulia Zanni, Hannah M. Deutsch, Phillip D. Rivera, Hung-Ying Shih, Junie A. LeBlanc, Wellington Z. Amaral, Melanie J. Lucero, Rachel L. Redfield, Matthew J. DeSalle, Benjamin P. C. Chen, Cody W. Whoolery, Ryan P. Reynolds, Sanghee Yun and Amelia J. Eisch
Int. J. Mol. Sci. 2018, 19(10), 3078; https://doi.org/10.3390/ijms19103078 - 09 Oct 2018
Cited by 11 | Viewed by 4873
Abstract
High-charge and -energy (HZE) particles comprise space radiation and they pose a challenge to astronauts on deep space missions. While exposure to most HZE particles decreases neurogenesis in the hippocampus—a brain structure important in memory—prior work suggests that 12C does not. However, [...] Read more.
High-charge and -energy (HZE) particles comprise space radiation and they pose a challenge to astronauts on deep space missions. While exposure to most HZE particles decreases neurogenesis in the hippocampus—a brain structure important in memory—prior work suggests that 12C does not. However, much about 12C’s influence on neurogenesis remains unknown, including the time course of its impact on neurogenesis. To address this knowledge gap, male mice (9–11 weeks of age) were exposed to whole-body 12C irradiation 100 cGy (IRR; 1000 MeV/n; 8 kEV/µm) or Sham treatment. To birthdate dividing cells, mice received BrdU i.p. 22 h post-irradiation and brains were harvested 2 h (Short-Term) or three months (Long-Term) later for stereological analysis indices of dentate gyrus neurogenesis. For the Short-Term time point, IRR mice had fewer Ki67, BrdU, and doublecortin (DCX) immunoreactive (+) cells versus Sham mice, indicating decreased proliferation (Ki67, BrdU) and immature neurons (DCX). For the Long-Term time point, IRR and Sham mice had similar Ki67+ and DCX+ cell numbers, suggesting restoration of proliferation and immature neurons 3 months post-12C irradiation. IRR mice had fewer surviving BrdU+ cells versus Sham mice, suggesting decreased cell survival, but there was no difference in BrdU+ cell survival rate when compared within treatment and across time point. These data underscore the ability of neurogenesis in the mouse brain to recover from the detrimental effect of 12C exposure. Full article
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25 pages, 1656 KiB  
Article
Transcriptional Homeostasis of Oxidative Stress-Related Pathways in Altered Gravity
by Svantje Tauber, Swantje Christoffel, Cora Sandra Thiel and Oliver Ullrich
Int. J. Mol. Sci. 2018, 19(9), 2814; https://doi.org/10.3390/ijms19092814 - 18 Sep 2018
Cited by 19 | Viewed by 3653
Abstract
Whereby several types of cultured cells are sensitive to gravity, the immune system belongs to the most affected systems during spaceflight. Since reactive oxygen species/reactive nitrogen species (ROS/RNS) are serving as signals of cellular homeostasis, particularly in the cells of the immune system, [...] Read more.
Whereby several types of cultured cells are sensitive to gravity, the immune system belongs to the most affected systems during spaceflight. Since reactive oxygen species/reactive nitrogen species (ROS/RNS) are serving as signals of cellular homeostasis, particularly in the cells of the immune system, we investigated the immediate effect of altered gravity on the transcription of 86 genes involved in reactive oxygen species metabolism, antioxidative systems, and cellular response to oxidative stress, using parabolic flight and suborbital ballistic rocket experiments and microarray analysis. In human myelomonocytic U937 cells, we detected a rapid response of 19.8% of all of the investigated oxidative stress-related transcripts to 1.8 g of hypergravity and 1.1% to microgravity as early as after 20 s. Nearly all (97.2%) of the initially altered transcripts adapted after 75 s of hypergravity (max. 13.5 g), and 100% adapted after 5 min of microgravity. After the almost complete adaptation of initially altered transcripts, a significant second pool of differentially expressed transcripts appeared. In contrast, we detected nearly no response of oxidative stress-related transcripts in human Jurkat T cells to altered gravity. In conclusion, we assume a very well-regulated homeostasis and transcriptional stability of oxidative stress-related pathways in altered gravity in cells of the human immune system. Full article
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15 pages, 4058 KiB  
Article
Impact of Spaceflight and Artificial Gravity on the Mouse Retina: Biochemical and Proteomic Analysis
by Xiao W. Mao, Stephanie Byrum, Nina C. Nishiyama, Michael J. Pecaut, Vijayalakshmi Sridharan, Marjan Boerma, Alan J. Tackett, Dai Shiba, Masaki Shirakawa, Satoru Takahashi and Michael D. Delp
Int. J. Mol. Sci. 2018, 19(9), 2546; https://doi.org/10.3390/ijms19092546 - 28 Aug 2018
Cited by 37 | Viewed by 9215
Abstract
Astronauts are reported to have experienced some impairment in visual acuity during their mission on the International Space Station (ISS) and after they returned to Earth. There is emerging evidence that changes in vision may involve alterations in ocular structure and function. To [...] Read more.
Astronauts are reported to have experienced some impairment in visual acuity during their mission on the International Space Station (ISS) and after they returned to Earth. There is emerging evidence that changes in vision may involve alterations in ocular structure and function. To investigate possible mechanisms, changes in protein expression profiles and oxidative stress-associated apoptosis were examined in mouse ocular tissue after spaceflight. Nine-week-old male C57BL/6 mice (n = 12) were launched from the Kennedy Space Center on a SpaceX rocket to the ISS for a 35-day mission. The animals were housed in the mouse Habitat Cage Unit (HCU) in the Japan Aerospace Exploration Agency (JAXA) “Kibo” facility on the ISS. The flight mice lived either under an ambient microgravity condition (µg) or in a centrifugal habitat unit that produced 1 g artificial gravity (µg + 1 g). Habitat control (HC) and vivarium control mice lived on Earth in HCUs or normal vivarium cages, respectively. Quantitative assessment of ocular tissue demonstrated that the µg group induced significant apoptosis in the retina vascular endothelial cells compared to all other groups (p < 0.05) that was 64% greater than that in the HC group. Proteomic analysis showed that many key pathways responsible for cell death, cell repair, inflammation, and metabolic stress were significantly altered in µg mice compared to HC animals. Additionally, there were more significant changes in regulated protein expression in the µg group relative to that in the µg + 1 g group. These data provide evidence that spaceflight induces retinal apoptosis of vascular endothelial cells and changes in retinal protein expression related to cellular structure, immune response and metabolic function, and that artificial gravity (AG) provides some protection against these changes. These retinal cellular responses may affect blood–retinal barrier (BRB) integrity, visual acuity, and impact the potential risk of developing late retinal degeneration. Full article
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Review

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26 pages, 304 KiB  
Review
Oxidative Stress as Cause, Consequence, or Biomarker of Altered Female Reproduction and Development in the Space Environment
by Jon G. Steller, Jeffrey R. Alberts and April E. Ronca
Int. J. Mol. Sci. 2018, 19(12), 3729; https://doi.org/10.3390/ijms19123729 - 23 Nov 2018
Cited by 46 | Viewed by 5898
Abstract
Oxidative stress has been implicated in the pathophysiology of numerous terrestrial disease processes and associated with morbidity following spaceflight. Furthermore, oxidative stress has long been considered a causative agent in adverse reproductive outcomes. The purpose of this review is to summarize the pathogenesis [...] Read more.
Oxidative stress has been implicated in the pathophysiology of numerous terrestrial disease processes and associated with morbidity following spaceflight. Furthermore, oxidative stress has long been considered a causative agent in adverse reproductive outcomes. The purpose of this review is to summarize the pathogenesis of oxidative stress caused by cosmic radiation and microgravity, review the relationship between oxidative stress and reproductive outcomes in females, and explore what role spaceflight-induced oxidative damage may have on female reproductive and developmental outcomes. Full article
14 pages, 539 KiB  
Review
Central Nervous System Responses to Simulated Galactic Cosmic Rays
by Egle Cekanaviciute, Susanna Rosi and Sylvain V. Costes
Int. J. Mol. Sci. 2018, 19(11), 3669; https://doi.org/10.3390/ijms19113669 - 20 Nov 2018
Cited by 71 | Viewed by 6113
Abstract
In preparation for lunar and Mars missions it is essential to consider the challenges to human health that are posed by long-duration deep space habitation via multiple stressors, including ionizing radiation, gravitational changes during flight and in orbit, other aspects of the space [...] Read more.
In preparation for lunar and Mars missions it is essential to consider the challenges to human health that are posed by long-duration deep space habitation via multiple stressors, including ionizing radiation, gravitational changes during flight and in orbit, other aspects of the space environment such as high level of carbon dioxide, and psychological stress from confined environment and social isolation. It remains unclear how these stressors individually or in combination impact the central nervous system (CNS), presenting potential obstacles for astronauts engaged in deep space travel. Although human spaceflight research only within the last decade has started to include the effects of radiation transmitted by galactic cosmic rays to the CNS, radiation is currently considered to be one of the main stressors for prolonged spaceflight and deep space exploration. Here we will review the current knowledge of CNS damage caused by simulated space radiation with an emphasis on neuronal and glial responses along with cognitive functions. Furthermore, we will present novel experimental approaches to integrate the knowledge into more comprehensive studies, including multiple stressors at once and potential translation to human functions. Finally, we will discuss the need for developing biomarkers as predictors for cognitive decline and therapeutic countermeasures to prevent CNS damage and the loss of cognitive abilities. Full article
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17 pages, 273 KiB  
Review
Oxidative Stress and the Kidney in the Space Environment
by Paraskevi Pavlakou, Evangelia Dounousi, Stefanos Roumeliotis, Theodoros Eleftheriadis and Vassilios Liakopoulos
Int. J. Mol. Sci. 2018, 19(10), 3176; https://doi.org/10.3390/ijms19103176 - 15 Oct 2018
Cited by 34 | Viewed by 4683
Abstract
In space, the special conditions of hypogravity and exposure to cosmic radiation have substantial differences compared to terrestrial circumstances, and a multidimensional impact on the human body and human organ functions. Cosmic radiation provokes cellular and gene damage, and the generation of reactive [...] Read more.
In space, the special conditions of hypogravity and exposure to cosmic radiation have substantial differences compared to terrestrial circumstances, and a multidimensional impact on the human body and human organ functions. Cosmic radiation provokes cellular and gene damage, and the generation of reactive oxygen species (ROS), leading to a dysregulation in the oxidants–antioxidants balance, and to the inflammatory response. Other practical factors contributing to these dysregulations in space environment include increased bone resorption, impaired anabolic response, and even difficulties in detecting oxidative stress in blood and urine samples. Enhanced oxidative stress affects mitochondrial and endothelial functions, contributes to reduced natriuresis and the development of hypertension, and may play an additive role in the formation of kidney stones. Finally, the composition of urine protein excretion is significantly altered, depicting possible tubular dysfunction. Full article
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18 pages, 570 KiB  
Review
Effects of Iron Overload and Oxidative Damage on the Musculoskeletal System in the Space Environment: Data from Spaceflights and Ground-Based Simulation Models
by Jiancheng Yang, Gejing Zhang, Dandan Dong and Peng Shang
Int. J. Mol. Sci. 2018, 19(9), 2608; https://doi.org/10.3390/ijms19092608 - 03 Sep 2018
Cited by 30 | Viewed by 5129
Abstract
The space environment chiefly includes microgravity and radiation, which seriously threatens the health of astronauts. Bone loss and muscle atrophy are the two most significant changes in mammals after long-term residency in space. In this review, we summarized current understanding of the effects [...] Read more.
The space environment chiefly includes microgravity and radiation, which seriously threatens the health of astronauts. Bone loss and muscle atrophy are the two most significant changes in mammals after long-term residency in space. In this review, we summarized current understanding of the effects of microgravity and radiation on the musculoskeletal system and discussed the corresponding mechanisms that are related to iron overload and oxidative damage. Furthermore, we enumerated some countermeasures that have a therapeutic potential for bone loss and muscle atrophy through using iron chelators and antioxidants. Future studies for better understanding the mechanism of iron and redox homeostasis imbalance induced by the space environment and developing the countermeasures against iron overload and oxidative damage consequently may facilitate human to travel more safely in space. Full article
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