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Oxidative Stress and Space Biology: An Organ-Based Approach

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 August 2017) | Viewed by 70381

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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, Europe and Japan have identified oxidative damage as a significant risk to major organs that could pose a threat to the health of the astronauts and the success of the mission. This Special Issue of IJMS is dedicated to providing a comprehensive overview of the identified risks and focus on how oxidative stress specifically could impact major organ systems when exposed to space-relevant conditions such as cosmic/galactic radiation, solar particle events, hypogravity, hyperoxia and hypoxia or a combination of stressors.

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

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Keywords

  • Cosmic radiation
  • Galactic radiation
  • Deep space exploration
  • Risk mitigation
  • Tissue toxicity

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Published Papers (11 papers)

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Editorial

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10 pages, 6168 KiB  
Editorial
Oxidative Stress and Space Biology: An Organ-Based Approach
by Thomas J. Goodwin and Melpo Christofidou-Solomidou
Int. J. Mol. Sci. 2018, 19(4), 959; https://doi.org/10.3390/ijms19040959 - 23 Mar 2018
Cited by 35 | Viewed by 5298
Abstract
The environment of space provides many challenges to the human physiology and therefore to extended habitation and exploration[...] Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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Research

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4834 KiB  
Article
Synthetic Secoisolariciresinol Diglucoside (LGM2605) Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage
by Anastasia Velalopoulou, Shampa Chatterjee, Ralph A. Pietrofesa, Cynthia Koziol-White, Reynold A. Panettieri, Liyong Lin, Stephen Tuttle, Abigail Berman, Constantinos Koumenis and Melpo Christofidou-Solomidou
Int. J. Mol. Sci. 2017, 18(12), 2525; https://doi.org/10.3390/ijms18122525 - 25 Nov 2017
Cited by 16 | Viewed by 4573
Abstract
Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known [...] Read more.
Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS), pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung. Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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2944 KiB  
Article
Combined Effects of Simulated Microgravity and Radiation Exposure on Osteoclast Cell Fusion
by Srinivasan Shanmugarajan, Ye Zhang, Maria Moreno-Villanueva, Ryan Clanton, Larry H. Rohde, Govindarajan T. Ramesh, Jean D. Sibonga and Honglu Wu
Int. J. Mol. Sci. 2017, 18(11), 2443; https://doi.org/10.3390/ijms18112443 - 18 Nov 2017
Cited by 22 | Viewed by 4947
Abstract
The loss of bone mass and alteration in bone physiology during space flight are one of the major health risks for astronauts. Although the lack of weight bearing in microgravity is considered a risk factor for bone loss and possible osteoporosis, organisms living [...] Read more.
The loss of bone mass and alteration in bone physiology during space flight are one of the major health risks for astronauts. Although the lack of weight bearing in microgravity is considered a risk factor for bone loss and possible osteoporosis, organisms living in space are also exposed to cosmic radiation and other environmental stress factors. As such, it is still unclear as to whether and by how much radiation exposure contributes to bone loss during space travel, and whether the effects of microgravity and radiation exposure are additive or synergistic. Bone is continuously renewed through the resorption of old bone by osteoclast cells and the formation of new bone by osteoblast cells. In this study, we investigated the combined effects of microgravity and radiation by evaluating the maturation of a hematopoietic cell line to mature osteoclasts. RAW 264.7 monocyte/macrophage cells were cultured in rotating wall vessels that simulate microgravity on the ground. Cells under static 1g or simulated microgravity were exposed to γ rays of varying doses, and then cultured in receptor activator of nuclear factor-κB ligand (RANKL) for the formation of osteoclast giant multinucleated cells (GMCs) and for gene expression analysis. Results of the study showed that radiation alone at doses as low as 0.1 Gy may stimulate osteoclast cell fusion as assessed by GMCs and the expression of signature genes such as tartrate resistant acid phosphatase (Trap) and dendritic cell-specific transmembrane protein (Dcstamp). However, osteoclast cell fusion decreased for doses greater than 0.5 Gy. In comparison to radiation exposure, simulated microgravity induced higher levels of cell fusion, and the effects of these two environmental factors appeared additive. Interestingly, the microgravity effect on osteoclast stimulatory transmembrane protein (Ocstamp) and Dcstamp expressions was significantly higher than the radiation effect, suggesting that radiation may not increase the synthesis of adhesion molecules as much as microgravity. Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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1768 KiB  
Article
Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System
by Joshua S. Alwood, Luan H. Tran, Ann-Sofie Schreurs, Yasaman Shirazi-Fard, Akhilesh Kumar, Diane Hilton, Candice G. T. Tahimic and Ruth K. Globus
Int. J. Mol. Sci. 2017, 18(10), 2117; https://doi.org/10.3390/ijms18102117 - 10 Oct 2017
Cited by 20 | Viewed by 4454
Abstract
Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation [...] Read more.
Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-weeks old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 MeV/n) or high-LET 56Fe ions (600 MeV/n) using either low (5 or 10 cGy) or high (50 or 200 cGy) doses at NASA’s Space Radiation Lab. Five weeks or one year after irradiation, tissues were harvested and analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed by RT-PCR during the proliferative or mineralizing phase of growth, and differentiation was analyzed by imaging mineralized nodules. As expected, a high dose (200 cGy), but not lower doses, of either 56Fe or protons caused a loss of cancellous bone volume/total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; 56Fe (200 cGy) inhibited osteoblastogenesis by more than 90% (5 weeks and 1 year post-IR). After 5 weeks, irradiation (protons or 56Fe) caused few changes in gene expression levels during osteoblastogenesis, although a high dose 56Fe (200 cGy) increased Catalase and Gadd45. The addition of exogenous superoxide dismutase (SOD) protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET (137Cs γ) when irradiated in vitro, but had limited protective effects on high-LET 56Fe-exposed cells. In sum, either protons or 56Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET 56Fe increased redox-related gene expression, albeit to a limited extent, and inhibited osteoblastogenesis. Doses below 50 cGy did not elicit widespread responses in any parameter measured. We conclude that high-LET irradiation at 200 cGy impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss. Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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6579 KiB  
Article
Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver
by Elizabeth A. Blaber, Michael J. Pecaut and Karen R. Jonscher
Int. J. Mol. Sci. 2017, 18(10), 2062; https://doi.org/10.3390/ijms18102062 - 27 Sep 2017
Cited by 45 | Viewed by 6860
Abstract
Increased oxidative stress is an unavoidable consequence of exposure to the space environment. Our previous studies showed that mice exposed to space for 13.5 days had decreased glutathione levels, suggesting impairments in oxidative defense. Here we performed unbiased, unsupervised and integrated multi-‘omic analyses [...] Read more.
Increased oxidative stress is an unavoidable consequence of exposure to the space environment. Our previous studies showed that mice exposed to space for 13.5 days had decreased glutathione levels, suggesting impairments in oxidative defense. Here we performed unbiased, unsupervised and integrated multi-‘omic analyses of metabolomic and transcriptomic datasets from mice flown aboard the Space Shuttle Atlantis. Enrichment analyses of metabolite and gene sets showed significant changes in osmolyte concentrations and pathways related to glycerophospholipid and sphingolipid metabolism, likely consequences of relative dehydration of the spaceflight mice. However, we also found increased enrichment of aminoacyl-tRNA biosynthesis and purine metabolic pathways, concomitant with enrichment of genes associated with autophagy and the ubiquitin-proteasome. When taken together with a downregulation in nuclear factor (erythroid-derived 2)-like 2-mediated signaling, our analyses suggest that decreased hepatic oxidative defense may lead to aberrant tRNA post-translational processing, induction of degradation programs and senescence-associated mitochondrial dysfunction in response to the spaceflight environment. Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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1057 KiB  
Article
Re-adaption on Earth after Spaceflights Affects the Mouse Liver Proteome
by Viktoria Anselm, Svetlana Novikova and Victor Zgoda
Int. J. Mol. Sci. 2017, 18(8), 1763; https://doi.org/10.3390/ijms18081763 - 12 Aug 2017
Cited by 23 | Viewed by 4179
Abstract
Harsh environmental conditions including microgravity and radiation during prolonged spaceflights are known to alter hepatic metabolism. Our studies have focused on the analysis of possible changes in metabolic pathways in the livers of mice from spaceflight project “Bion-M 1”. Mice experienced 30 days [...] Read more.
Harsh environmental conditions including microgravity and radiation during prolonged spaceflights are known to alter hepatic metabolism. Our studies have focused on the analysis of possible changes in metabolic pathways in the livers of mice from spaceflight project “Bion-M 1”. Mice experienced 30 days of spaceflight with and without an additional re-adaption period of seven days compared to control mice on Earth. To investigate mice livers we have performed proteomic profiling utilizing shotgun mass spectrometry followed by label-free quantification. Proteomic data analysis provided 12,206 unique peptides and 1,086 identified proteins. Label-free quantification using MaxQuant software followed by multiple sample statistical testing (ANOVA) revealed 218 up-regulated and 224 down-regulated proteins in the post-flight compared to the other groups. Proteins related to amino acid metabolism showed higher levels after re-adaption, which may indicate higher rates of gluconeogenesis. Members of the peroxisome proliferator-activated receptor pathway reconstitute their level after seven days based on a decreased level in comparison with the flight group, which indicates diminished liver lipotoxicity. Moreover, bile acid secretion may regenerate on Earth due to reconstitution of related transmembrane proteins and CYP superfamily proteins elevated levels seven days after the spaceflight. Thus, our study demonstrates reconstitution of pharmacological response and decreased liver lipotoxicity within seven days, whereas glucose uptake should be monitored due to alterations in gluconeogenesis. Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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10064 KiB  
Article
Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury
by Stefanie Endesfelder, Ulrike Weichelt, Evelyn Strauß, Anja Schlör, Marco Sifringer, Till Scheuer, Christoph Bührer and Thomas Schmitz
Int. J. Mol. Sci. 2017, 18(1), 187; https://doi.org/10.3390/ijms18010187 - 18 Jan 2017
Cited by 82 | Viewed by 8102
Abstract
Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, [...] Read more.
Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28–32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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Review

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5062 KiB  
Review
Metabolic Pathways of the Warburg Effect in Health and Disease: Perspectives of Choice, Chain or Chance
by Jorge S. Burns and Gina Manda
Int. J. Mol. Sci. 2017, 18(12), 2755; https://doi.org/10.3390/ijms18122755 - 19 Dec 2017
Cited by 117 | Viewed by 12963
Abstract
Focus on the Warburg effect, initially descriptive of increased glycolysis in cancer cells, has served to illuminate mitochondrial function in many other pathologies. This review explores our current understanding of the Warburg effect’s role in cancer, diabetes and ageing. We highlight how it [...] Read more.
Focus on the Warburg effect, initially descriptive of increased glycolysis in cancer cells, has served to illuminate mitochondrial function in many other pathologies. This review explores our current understanding of the Warburg effect’s role in cancer, diabetes and ageing. We highlight how it can be regulated through a chain of oncogenic events, as a chosen response to impaired glucose metabolism or by chance acquisition of genetic changes associated with ageing. Such chain, choice or chance perspectives can be extended to help understand neurodegeneration, such as Alzheimer’s disease, providing clues with scope for therapeutic intervention. It is anticipated that exploration of Warburg effect pathways in extreme conditions, such as deep space, will provide further insights crucial for comprehending complex metabolic diseases, a frontier for medicine that remains equally significant for humanity in space and on earth. Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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732 KiB  
Review
Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight
by Candice G. T. Tahimic and Ruth K. Globus
Int. J. Mol. Sci. 2017, 18(10), 2153; https://doi.org/10.3390/ijms18102153 - 16 Oct 2017
Cited by 20 | Viewed by 5139
Abstract
Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level [...] Read more.
Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and ground-based models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function. Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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1327 KiB  
Review
The Impact of Oxidative Stress on the Bone System in Response to the Space Special Environment
by Ye Tian, Xiaoli Ma, Chaofei Yang, Peihong Su, Chong Yin and Ai-Rong Qian
Int. J. Mol. Sci. 2017, 18(10), 2132; https://doi.org/10.3390/ijms18102132 - 12 Oct 2017
Cited by 52 | Viewed by 6900
Abstract
The space special environment mainly includes microgravity, radiation, vacuum and extreme temperature, which seriously threatens an astronaut’s health. Bone loss is one of the most significant alterations in mammalians after long-duration habitation in space. In this review, we summarize the crucial roles of [...] Read more.
The space special environment mainly includes microgravity, radiation, vacuum and extreme temperature, which seriously threatens an astronaut’s health. Bone loss is one of the most significant alterations in mammalians after long-duration habitation in space. In this review, we summarize the crucial roles of major factors—namely radiation and microgravity—in space in oxidative stress generation in living organisms, and the inhibitory effect of oxidative stress on bone formation. We discussed the possible mechanisms of oxidative stress-induced skeletal involution, and listed some countermeasures that have therapeutic potentials for bone loss via oxidative stress antagonism. Future research for better understanding the oxidative stress caused by space environment and the development of countermeasures against oxidative damage accordingly may facilitate human beings to live more safely in space and explore deeper into the universe. Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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390 KiB  
Review
Effect of Oxidative Stress on Cardiovascular System in Response to Gravity
by Ken Takahashi, Hiroki Okumura, Rui Guo and Keiji Naruse
Int. J. Mol. Sci. 2017, 18(7), 1426; https://doi.org/10.3390/ijms18071426 - 04 Jul 2017
Cited by 33 | Viewed by 6331
Abstract
Long-term habitation in space leads to physiological alterations such as bone loss, muscle atrophy, and cardiovascular deconditioning. Two predominant factors—namely space radiation and microgravity—have a crucial impact on oxidative stress in living organisms. Oxidative stress is also involved in the aging process, and [...] Read more.
Long-term habitation in space leads to physiological alterations such as bone loss, muscle atrophy, and cardiovascular deconditioning. Two predominant factors—namely space radiation and microgravity—have a crucial impact on oxidative stress in living organisms. Oxidative stress is also involved in the aging process, and plays important roles in the development of cardiovascular diseases including hypertension, left ventricular hypertrophy, and myocardial infarction. Here, we discuss the effects of space radiation, microgravity, and a combination of these two factors on oxidative stress. Future research may facilitate safer living in space by reducing the adverse effects of oxidative stress. Full article
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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