Changes in muscle cell proteostasis by mechanical stress induced by altered gravity conditions

Abstract

Autophagy is a central process in regards to homeostasis in most cells. Here, CASA, as a chaperone-mediated autophagic pathway, plays a particularly complex and important role. Furthermore, the central co-chaperone BAG3 allows for interactions with multiple other cellular mechanisms due to its multi-domain structure. The application of simulated microgravity as a model for complete mechanical unloading could potentially lead to better comprehension of the versatile autophagic mechanism in the future. Moreover, a deeper understanding of the gravitation dependent regulation of CASA in skeletal muscle cells could help to develop novel therapeutic countermeasures to mitigate the formation of spaceflight-induced muscle atrophy in astronauts. In this thesis, it was shown that the CASA-associated proteins BAG3, HSPB8, FLNC and STK38 exhibit temporal regulations as a response to simulated microgravity and hypergravity exposure by conducting different time series and biochemical analyses. Especially FLNC was shown to be specifically regulated as a result of the different experimental setups under altered gravity exposure. These outcomes partially correlated with results of the other investigated proteins and could thus be explained plausibly. Some of the results indicated that using simulated microgravity as a model to create baseline values by mechanically unloading muscle cells might indeed be a plausible approach. However, further studies are required to properly declare the approach as useful and functional. In addition, several specific phenotypes of C2 skeletal muscle cells were observed, which develop due to the exposure to simulated microgravity or hypergravity.