Gene‐Metabolite Network Linked to Inhibited Bioenergetics in Association With Spaceflight‐Induced Loss of Male Mouse Quadriceps Muscle
Autor: | Nabarun Chakraborty, Paul Childress, Michael Savaglio, George Dimitrov, Allison Hoke, Aarti Gautam, Bintu Sowe, David L. Waning, Raina Kumar, Rasha Hammamieh, Dana Youssef, Candace Moyler, Melissa A. Kacena, Stephan Butler |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism ANIMAL MODEL METABOLISM Carbohydrate metabolism Biology medicine.disease_cause Spaceflight Sarcomere Quadriceps Muscle law.invention Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine law Internal medicine Myosin medicine Animals Orthopedics and Sports Medicine RNA Messenger Weightlessness Skeletal muscle Original Articles Space Flight Muscle atrophy TISSUE SIGNALING Mice Inbred C57BL Muscular Atrophy 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry SYSTEMS BIOLOGY Metabolome Original Article medicine.symptom SKELETAL MUSCLE Adenosine triphosphate Oxidative stress |
Zdroj: | Journal of Bone and Mineral Research |
ISSN: | 1523-4681 0884-0431 |
Popis: | 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 inhibited networks related to protein, lipid, and carbohydrate metabolism, and adenosine triphosphate (ATP) synthesis and hydrolysis. Finally, we discovered important upstream regulators, which could be targeted for next‐generation therapeutic intervention for chronic disuse of the musculoskeletal system. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research. |
Databáze: | OpenAIRE |
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