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

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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.


Protein abundance is altered in cardiomyocytes during simulated microgravity.(A) Principal components analysis (PCA) was performed using protein data from Supplemental Table S3, z-score normalized. The smallest variability among any sample group is among 0 h and 12 h samples, followed by 48 h and 120 h. The QC pool samples are nearly indistinguishable in the center of the PCA, showing technical variability is far less than biological variability. (B) Fraction of proteins that changed as a function of time or between groups.
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f2: Protein abundance is altered in cardiomyocytes during simulated microgravity.(A) Principal components analysis (PCA) was performed using protein data from Supplemental Table S3, z-score normalized. The smallest variability among any sample group is among 0 h and 12 h samples, followed by 48 h and 120 h. The QC pool samples are nearly indistinguishable in the center of the PCA, showing technical variability is far less than biological variability. (B) Fraction of proteins that changed as a function of time or between groups.

Mentions: Intensity values for 6,174 peptides (Supplemental Table 2; peptide expression) were utilized to measure the relative expression for 848 proteins across all time points (0, 12, 48, and 120 h) and gravity conditions (μg or 1xg) (Supplemental Table 3; protein expression). Principal components analysis (PCA) demonstrated that as a whole, protein abundance between μg and 1xg samples were not different at 12 h, only slightly different at 48 h, and highly different at 120 h (Fig. 2A).


Microgravity induces proteomics changes involved in endoplasmic reticulum stress and mitochondrial protection
Protein abundance is altered in cardiomyocytes during simulated microgravity.(A) Principal components analysis (PCA) was performed using protein data from Supplemental Table S3, z-score normalized. The smallest variability among any sample group is among 0 h and 12 h samples, followed by 48 h and 120 h. The QC pool samples are nearly indistinguishable in the center of the PCA, showing technical variability is far less than biological variability. (B) Fraction of proteins that changed as a function of time or between groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Protein abundance is altered in cardiomyocytes during simulated microgravity.(A) Principal components analysis (PCA) was performed using protein data from Supplemental Table S3, z-score normalized. The smallest variability among any sample group is among 0 h and 12 h samples, followed by 48 h and 120 h. The QC pool samples are nearly indistinguishable in the center of the PCA, showing technical variability is far less than biological variability. (B) Fraction of proteins that changed as a function of time or between groups.
Mentions: Intensity values for 6,174 peptides (Supplemental Table 2; peptide expression) were utilized to measure the relative expression for 848 proteins across all time points (0, 12, 48, and 120 h) and gravity conditions (μg or 1xg) (Supplemental Table 3; protein expression). Principal components analysis (PCA) demonstrated that as a whole, protein abundance between μg and 1xg samples were not different at 12 h, only slightly different at 48 h, and highly different at 120 h (Fig. 2A).

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.