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Int. J. Mol. Sci. 2017, 18(10), 2062; doi:10.3390/ijms18102062

Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver

1
Universities Space Research Association, Mountain View, CA 94040, USA
2
NASA Ames Research Center, Moffett Field, CA 94035, USA
3
Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA
4
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
*
Author to whom correspondence should be addressed.
Received: 31 August 2017 / Revised: 13 September 2017 / Accepted: 13 September 2017 / Published: 27 September 2017
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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Abstract

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. View Full-Text
Keywords: spaceflight; autophagy; proteasome; metabolomics; tRNA biosynthesis; senescence spaceflight; autophagy; proteasome; metabolomics; tRNA biosynthesis; senescence
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Blaber, E.A.; Pecaut, M.J.; Jonscher, K.R. Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver. Int. J. Mol. Sci. 2017, 18, 2062.

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