Microgravity induces proteomics changes involved in endoplasmic reticulum stress and mitochondrial protection.
On Earth, biological systems have evolved in response to environmental stressors, interactions dictated by physical forces that include gravity. The absence of gravity is an extreme stressor and the impact of its absence on biological systems is ill-defined. Astronauts who have spent extended time under conditions of minimal gravity (microgravity) experience an array of biological alterations, including perturbations in cardiovascular function. We hypothesized that physiological perturbations in cardiac function in microgravity may be a consequence of alterations in molecular and organellar dynamics within the cellular milieu of cardiomyocytes. We used a combination of mass spectrometry-based approaches to compare the relative abundance and turnover rates of 848 and 196 proteins, respectively, in rat neonatal cardiomyocytes exposed to simulated microgravity or normal gravity. Gene functional enrichment analysis of these data suggested that the protein content and function of the mitochondria, ribosomes, and endoplasmic reticulum were differentially modulated in microgravity. We confirmed experimentally that in microgravity protein synthesis was decreased while apoptosis, cell viability, and protein degradation were largely unaffected. These data support our conclusion that in microgravity cardiomyocytes attempt to maintain mitochondrial homeostasis at the expense of protein synthesis. The overall response to this stress may culminate in cardiac muscle atrophy.
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Bryan J
BJ
Feger
Duke Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27710, USA.
J Will
JW
Thompson
Duke Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27710, USA.
Laura G
LG
Dubois
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Reddy P
RP
Kommaddi
Duke Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27710, USA.|Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Matthew W
MW
Foster
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Rajashree
R
Mishra
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Sudha K
SK
Shenoy
Department of Genetics, the Carolina Center for Genome Sciences, and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Yoichiro
Y
Shibata
Wyle Science, Technology and Engineering Group, Houston, TX 77058, USA.|NASA Johnson Space Center, Houston, TX 77058, USA.
Yared H
YH
Kidane
Duke Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27710, USA.
M Arthur
MA
Moseley
NASA Langley Research Center, Hampton, VA, 23666, USA.
Lisa S
LS
Carnell
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Dawn E
DE
Bowles
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