Gene-Metabolite Network Linked to Inhibited Bioenergetics in Association With Spaceflight-Induced Loss of Male Mouse Quadriceps Muscle.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Nabarun ChakrabortyRasha Hammamieh

Abstract

Prolonged residence of mice in spaceflight is a scientifically robust and ethically ratified model of muscle atrophy caused by continued unloading. Under the Rodent Research Program of the National Aeronautics and Space Administration (NASA), we assayed the large-scale mRNA and metabolomic perturbations in the quadriceps of C57BL/6j male mice that lived in spaceflight (FLT) or on the ground (control or CTR) for approximately 4 weeks. The wet weights of the quadriceps were significantly reduced in FLT mice. Next-generation sequencing and untargeted mass spectroscopic assays interrogated the gene-metabolite landscape of the quadriceps. A majority of top-ranked differentially suppressed genes in FLT encoded proteins from the myosin or troponin families, suggesting sarcomere alterations in space. Significantly enriched gene-metabolite networks were found linked to sarcomeric integrity, immune fitness, and oxidative stress response; all inhibited in space as per in silico prediction. A significant loss of mitochondrial DNA copy numbers in FLT mice underlined the energy deprivation associated with spaceflight-induced stress. This hypothesis was reinforced by the transcriptomic sequencing-metabolomics integrative analysis that showed ...Continue Reading

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Citations

Apr 10, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yuhei UdaPaola Divieti Pajevic
Jul 2, 2021·Computational and Structural Biotechnology Journal·Nabarun ChakrabortyMelissa A Kacena
Aug 28, 2021·International Journal of Molecular Sciences·Akhilesh KumarRuth K Globus
Aug 27, 2021·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Adam M KnoxChristopher D Collier

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Methods Mentioned

BETA
ISS
ELISA

Software Mentioned

FLT
R scripts
Ingenuity Pathway Analysis
ImPala
IPA
R

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