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 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 1086 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.
Highlights
Spaceflights provide a unique opportunity to study microgravity-related changes in organs on a biochemical level
Open questions on the proteome dynamics during prolonged spaceflights and their effect on this vital organ involved in metabolism is of great clinical interest in terms of therapy and medical monitoring
Questions about the impact of environmental conditions during spaceflights can be addressed testing model organisms such as mice. One of these questions is how long-term adaption to spaceflight environment and re-adaption to Earth is reflected in the liver proteome
Summary
Spaceflights provide a unique opportunity to study microgravity-related changes in organs on a biochemical level. The level of 10 quantified and bile secretion related proteins (Table 2) is significantly lower in post-flight than in the flight or control group (ANOVA test, FDR = 0.05). The majority of these proteins have ion or cation transporter activity to regulate the bile flow from liver to gall bladder by building an osmotic gradient [9]. There was no difference in the abundance of these transmembrane proteins between the control and flight group, which could be owed to less sensitive fold change detection between flight and control This could be caused by the high significance threshold observed with multiple testing correction using permutation based FDR (Figure S1, A). No significant difference in cytochromes profile between control and post-flight shows that re-adaption to the usual drug metabolizing CYP levels occurs within seven days after landing
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