Correction: Spaceflight Activates Lipotoxic Pathways in Mouse Liver.
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ABSTRACT:
SUBMITTER: Jonscher KR
PROVIDER: S-EPMC4856369 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
Correction: Spaceflight Activates Lipotoxic Pathways in Mouse Liver.
Jonscher Karen R KR Alfonso-Garcia Alba A Suhalim Jeffrey L JL Orlicky David J DJ Potma Eric O EO Ferguson Virginia L VL Bouxsein Mary L ML Bateman Ted A TA Stodieck Louis S LS Levi Moshe M Friedman Jacob E JE Gridley Daila S DS Pecaut Michael J MJ
PloS one 20160504 5
[This corrects the article DOI: 10.1371/journal.pone.0152877.]. ...[more]
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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.
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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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