Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver.
Elizabeth A BlaberMichael J PecautKaren R JonscherPublished in: International journal of molecular sciences (2017)
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.
Keyphrases
- oxidative stress
- nuclear factor
- high fat diet induced
- signaling pathway
- cell death
- dna damage
- toll like receptor
- endoplasmic reticulum stress
- machine learning
- small molecule
- cell proliferation
- copy number
- rna seq
- insulin resistance
- wild type
- inflammatory response
- induced apoptosis
- type diabetes
- single cell
- adipose tissue
- metabolic syndrome
- innate immune
- dna methylation