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Microgravity induces proteomics changes involved in endoplasmic reticulum stress and mitochondrial protection

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Gene Ontology.(A) Comparison of enrichment of Gene Ontology cellular components for protein abundance and turnover data sets. (B) Leading genes that contributed to the difference and similarity in the perturbation of the cellular components shown in panel A. A 0.05 FDR cutoff value was used for this analysis.
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f4: Gene Ontology.(A) Comparison of enrichment of Gene Ontology cellular components for protein abundance and turnover data sets. (B) Leading genes that contributed to the difference and similarity in the perturbation of the cellular components shown in panel A. A 0.05 FDR cutoff value was used for this analysis.

Mentions: The analysis of the combination of abundance and turnover data revealed that the mitochondria was more impacted than other organelles in the cell (Fig. 4A). However, it appears that mitochondrial turnover was more impacted than protein abundance. A total of 40 proteins from both data sets mapped to these mitochondrial processes (Fig. 4B). Two proteins were unique to the abundance data set, 13 were unique to the turnover data, and 25 proteins were common to both data sets. We mapped these common genes to pathways using the Pathway Commons database (results not shown here). The top significant pathways include the citric acid cycle (TCA), ATP synthesis, nuclear estrogen receptor network, and metabolism of carbohydrates, amino acids, and glucose.


Microgravity induces proteomics changes involved in endoplasmic reticulum stress and mitochondrial protection
Gene Ontology.(A) Comparison of enrichment of Gene Ontology cellular components for protein abundance and turnover data sets. (B) Leading genes that contributed to the difference and similarity in the perturbation of the cellular components shown in panel A. A 0.05 FDR cutoff value was used for this analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037457&req=5

f4: Gene Ontology.(A) Comparison of enrichment of Gene Ontology cellular components for protein abundance and turnover data sets. (B) Leading genes that contributed to the difference and similarity in the perturbation of the cellular components shown in panel A. A 0.05 FDR cutoff value was used for this analysis.
Mentions: The analysis of the combination of abundance and turnover data revealed that the mitochondria was more impacted than other organelles in the cell (Fig. 4A). However, it appears that mitochondrial turnover was more impacted than protein abundance. A total of 40 proteins from both data sets mapped to these mitochondrial processes (Fig. 4B). Two proteins were unique to the abundance data set, 13 were unique to the turnover data, and 25 proteins were common to both data sets. We mapped these common genes to pathways using the Pathway Commons database (results not shown here). The top significant pathways include the citric acid cycle (TCA), ATP synthesis, nuclear estrogen receptor network, and metabolism of carbohydrates, amino acids, and glucose.

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.