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.

Designing a Novel Monitoring Approach for the Effects of Space Travel on Astronauts’ Health

“…However, these tumors may be less malignant or even benign [ 22 , 23 , 24 ]. Moreover, consistent with previous studies [ 54 , 55 ], our results showed that space travel significantly affects astronauts’ liver function and liver metabolism. Key genes identified from our analysis, such as GPT and UBA5 , might serve as valuable monitoring biomarkers of astronauts’ liver function and even possible medical intervention points to protect astronauts’ health.…”

Designing a novel monitoring approach for the effects of space travel on astronauts’ health

“…e ., reduced gene expression correlation) we observed in this study, other than compromised immune function, is likely to play an important role in tumor development in astronauts, even though the tumors may be less malignant or even benign. Moreover, consistent with previous studies 46,47 , our results showed that space travel significantly affects astronauts’ liver function and liver metabolism. Key genes identified from our analysis, such as GPT and UBA5 , might serve as valuable monitoring biomarkers of astronauts’ liver function and even possible medical intervention points to protect astronauts’ health.…”

Investigating the effects of chronic low-dose radiation exposure in the liver of a hypothermic zebrafish model

“…It revealed 52 shared orthologues and the shared upregulation of genes involved in fibroblast growth factor-activated receptor activity (FGFR3) (GO:0005007), suggesting radiation-induced fibrogenesis, and NEU1 involved in cell migration. The mice also showed the upregulation of sulphur dioxygenase activity ( ETHE1 ) (GO:0050313), consistent with spaceflight-induced changes to sulphur metabolism 65 . On the contrary, shared downregulated genes include ROBO2, which is involved in hepatic stellate cell activation, and KANK1, which is involved in cytoskeleton formation.…”