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Impact of spaceflight and artificial gravity on sulfur metabolism in mouse liver: sulfur metabolomic and transcriptomic analysis

ABSTRACT: Spaceflight induces hepatic damage, partially owing to oxidative stress caused by the space environment such as microgravity and space radiation. We examined the roles of anti-oxidative sulfur-containing compounds on hepatic damage after spaceflight. We analyzed the livers of mice on board the International Space Station for 30 days. During spaceflight, half of the mice were exposed to artificial earth gravity (1 g) using centrifugation cages. Sulfur-metabolomics of the livers of mice after spaceflight revealed a decrease in sulfur antioxidants (ergothioneine, glutathione, cysteine, taurine, thiamine, etc.) and their intermediates (cysteine sulfonic acid, hercynine, N-acethylserine, serine, etc.) compared to the controls on the ground. Furthermore, RNA-sequencing showed upregulation of gene sets related to oxidative stress and sulfur metabolism, and downregulation of gene sets related to glutathione reducibility in the livers of mice after spaceflight, compared to controls on the ground. These changes were partially mitigated by exposure to 1 g centrifugation. For the first time, we observed a decrease in sulfur antioxidants based on a comprehensive analysis of the livers of mice after spaceflight. Our data suggest that a decrease in sulfur-containing compounds owing to both microgravity and other spaceflight environments (radiation and stressors) contributes to liver damage after spaceflight.

SUBMITTER: Kurosawa R

PROVIDER: S-EPMC8575787 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Impact of spaceflight and artificial gravity on sulfur metabolism in mouse liver: sulfur metabolomic and transcriptomic analysis

Project description:Spaceflight induces hepatic damage, partially owing to oxidative stress caused by the space environment such as microgravity and space radiation. We examined the roles of anti-oxidative sulfur-containing compounds on hepatic damage after spaceflight. We analyzed the livers of mice on board the International Space Station for 30 days. During spaceflight, half of the mice were exposed to artificial earth gravity (1 g) using centrifugation cages. Sulfur-metabolomics of the livers of mice after spaceflight revealed a decrease in sulfur antioxidants (ergothioneine, glutathione, cysteine, taurine, thiamine, etc.) and their intermediates (cysteine sulfonic acid, hercynine, N-acethylserine, serine, etc.) compared to the controls on the ground. Furthermore, RNA-sequencing showed upregulation of gene sets related to oxidative stress and sulfur metabolism, and downregulation of gene sets related to glutathione reducibility in the livers of mice after spaceflight, compared to controls on the ground. These changes were partially mitigated by exposure to 1 g centrifugation. For the first time, we observed a decrease in sulfur antioxidants based on a comprehensive analysis of the livers of mice after spaceflight. Our data suggest that a decrease in sulfur-containing compounds owing to both microgravity and other spaceflight environments (radiation and stressors) contributes to liver damage after spaceflight.

2023-08-14 | GSE240751 | GEO

Impact of spaceflight and artificial gravity on sulfur metabolism in mouse liver: sulfur metabolomic and transcriptomic analysis

Project description:Impact of spaceflight and artificial gravity on sulfur metabolism in mouse liver: sulfur metabolomic and transcriptomic analysis

| PRJNA1005192 | ENA

Impact of spaceflight on the murine thymus and mitigation by exposure to artificial gravity during spaceflight.

Project description:The environment experienced during spaceflight may impact the immune system and the thymus appears to undergo atrophy during spaceflight. However, molecular aspects of this thymic atrophy remain to be elucidated. In this study, we analysed the thymi of mice on board the international space station (ISS) for approximately 1 month. Thymic size was significantly reduced after spaceflight. Notably, exposure of mice to 1?×?g using centrifugation cages in the ISS significantly mitigated the reduction in thymic size. Although spaceflight caused thymic atrophy, the global thymic structure was not largely changed. However, RNA sequencing analysis of the thymus showed significantly reduced expression of cell cycle-regulating genes in two independent spaceflight samples. These reductions were partially countered by 1?×?g exposure during the space flights. Thus, our data suggest that spaceflight leads to reduced proliferation of thymic cells, thereby reducing the size of the thymus, and exposure to 1?×?g might alleviate the impairment of thymus homeostasis induced by spaceflight.

| S-EPMC6934594 | biostudies-literature

Spaceflight Activates Lipotoxic Pathways in Mouse Liver.

Project description:Spaceflight affects numerous organ systems in the body, leading to metabolic dysfunction that may have long-term consequences. Microgravity-induced alterations in liver metabolism, particularly with respect to lipids, remain largely unexplored. Here we utilize a novel systems biology approach, combining metabolomics and transcriptomics with advanced Raman microscopy, to investigate altered hepatic lipid metabolism in mice following short duration spaceflight. Mice flown aboard Space Transportation System -135, the last Shuttle mission, lose weight but redistribute lipids, particularly to the liver. Intriguingly, spaceflight mice lose retinol from lipid droplets. Both mRNA and metabolite changes suggest the retinol loss is linked to activation of PPAR?-mediated pathways and potentially to hepatic stellate cell activation, both of which may be coincident with increased bile acids and early signs of liver injury. Although the 13-day flight duration is too short for frank fibrosis to develop, the retinol loss plus changes in markers of extracellular matrix remodeling raise the concern that longer duration exposure to the space environment may result in progressive liver damage, increasing the risk for nonalcoholic fatty liver disease.

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Correction: Spaceflight Activates Lipotoxic Pathways in Mouse Liver.

Project description:[This corrects the article DOI: 10.1371/journal.pone.0152877.].

| S-EPMC4856369 | biostudies-literature

Spaceflight Effects on Cytochrome P450 Content in Mouse Liver.

Project description:Hard conditions of long-term manned spaceflight can affect functions of many biological systems including a system of drug metabolism. The cytochrome P450 (CYP) superfamily plays a key role in the drug metabolism. In this study we examined the hepatic content of some P450 isoforms in mice exposed to 30 days of space flight and microgravity. The CYP content was established by the mass-spectrometric method of selected reaction monitoring (SRM). Significant changes in the CYP2C29, CYP2E1 and CYP1A2 contents were detected in mice of the flight group compared to the ground control group. Within seven days after landing and corresponding recovery period changes in the content of CYP2C29 and CYP1A2 returned to the control level, while the CYP2E1 level remained elevated. The induction of enzyme observed in the mice in the conditions of the spaceflight could lead to an accelerated biotransformation and change in efficiency of pharmacological agents, metabolizing by corresponding CYP isoforms. Such possibility of an individual pharmacological response to medication during long-term spaceflights and early period of postflight adaptation should be taken into account in space medicine.

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Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver.

Project description: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.

| S-EPMC5666744 | biostudies-other

Assessing the effects of artificial gravity in an analog of long-duration spaceflight: The protocol and implementation of the AGBRESA bed rest study.

Project description:A comprehensive strategy is required to mitigate risks to astronauts' health, well-being, and performance. This strategy includes developing countermeasures to prevent or reduce adverse responses to the stressors astronauts encounter during spaceflight, such as weightlessness. Because artificial gravity (AG) by centrifugation simultaneously affects all physiological systems, AG could mitigate the effects of weightlessness in multiple systems. In 2019, NASA and the German Aerospace Center conducted a 60-days Artificial Gravity Bed Rest Study with the European Space Agency (AGBRESA). The objectives of this study were to 1) determine if 30 min of AG daily is protective during head down bed rest, and 2) compare the protective effects of a single daily bout (30 min) of AG versus multiple daily bouts (6 × 5 min) of AG (1 Gz at the center of mass) on physiological functions that are affected by weightlessness and by head-down tilt bed rest. The AGBRESA study involved a comprehensive suite of standard and innovative technologies to characterize changes in a broad spectrum of physiological systems. The current article is intended to provide a detailed overview of the methods used during AGBRESA.

| S-EPMC9492851 | biostudies-literature

Toll mediated infection response is altered by gravity and spaceflight in Drosophila.

Project description:Space travel presents unlimited opportunities for exploration and discovery, but requires better understanding of the biological consequences of long-term exposure to spaceflight. Immune function in particular is relevant for space travel. Human immune responses are weakened in space, with increased vulnerability to opportunistic infections and immune-related conditions. In addition, microorganisms can become more virulent in space, causing further challenges to health. To understand these issues better and to contribute to design of effective countermeasures, we used the Drosophila model of innate immunity to study immune responses in both hypergravity and spaceflight. Focusing on infections mediated through the conserved Toll and Imd signaling pathways, we found that hypergravity improves resistance to Toll-mediated fungal infections except in a known gravitaxis mutant of the yuri gagarin gene. These results led to the first spaceflight project on Drosophila immunity, in which flies that developed to adulthood in microgravity were assessed for immune responses by transcription profiling on return to Earth. Spaceflight alone altered transcription, producing activation of the heat shock stress system. Space flies subsequently infected by fungus failed to activate the Toll pathway. In contrast, bacterial infection produced normal activation of the Imd pathway. We speculate on possible linkage between functional Toll signaling and the heat shock chaperone system. Our major findings are that hypergravity and spaceflight have opposing effects, and that spaceflight produces stress-related transcriptional responses and results in a specific inability to mount a Toll-mediated infection response.

| S-EPMC3901686 | biostudies-literature

The integrative metabolomic-transcriptomic landscape of glioblastome multiforme.

Project description:The purpose of this study was to map the landscape of metabolic-transcriptional alterations in glioblastoma multiforme. Omic-datasets were acquired by metabolic profiling (1D-NMR spectroscopy n=33 Patient) and transcriptomic profiling (n=48 Patients). Both datasets were analyzed by integrative network modeling. The computed model concluded in four different metabolic-transcriptomic signatures containing: oligodendrocytic differentiation, cell-cycle functions, immune response and hypoxia. These clusters were found being distinguished by individual metabolism and distinct transcriptional programs. The study highlighted the association between metabolism and hallmarks of oncogenic signaling such as cell-cycle alterations, immune escape mechanism and other cancer pathway alterations. In conclusion, this study showed the strong influence of metabolic alterations in the wide scope of oncogenic transcriptional alterations.

| S-EPMC5564759 | biostudies-other

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