A deep analysis of the proteomic and phosphoproteomic alterations that occur in skeletal muscle after the onset of immobilization.
Kuan-Hung LinGary M WilsonRocky BlancoNathaniel D SteinertWenyuan G ZhuJoshua J CoonTroy A HornbergerPublished in: The Journal of physiology (2021)
The disuse of skeletal muscle, such as that which occurs during immobilization, can lead to the rapid loss of muscle mass, and a decrease in the rate of protein synthesis plays a major role in this process. Indeed, current dogma contends that the decrease in protein synthesis is mediated by changes in the activity of protein kinases (e.g. mTOR); however, the validity of this model has not been established. Therefore, to address this, we first subjected mice to 6, 24 or 72 h of unilateral immobilization and then used the SUnSET technique to measure changes in the relative rate of protein synthesis. The result of our initial experiments revealed that immobilization leads to a rapid (within 6 h) and progressive decrease in the rate of protein synthesis and that this effect is mediated by a decrease in translational efficiency. We then performed a deep mass spectrometry-based analysis to determine whether this effect could be explained by changes in the expression and/or phosphorylation state of proteins that regulate translation. From this analysis, we were able to quantify 4320 proteins and 15,020 unique phosphorylation sites, and surprisingly, the outcomes revealed that the rapid immobilization-induced decrease in protein synthesis could not be explained by changes in either the abundance, or phosphorylation state, of proteins. The results of our work not only challenge the current dogma in the field, but also provide an expansive resource of information for future studies that are aimed at defining how disuse leads to loss of muscle mass.
Keyphrases
- skeletal muscle
- mass spectrometry
- insulin resistance
- magnetic nanoparticles
- multiple sclerosis
- loop mediated isothermal amplification
- protein kinase
- poor prognosis
- single cell
- type diabetes
- healthcare
- metabolic syndrome
- adipose tissue
- current status
- social media
- high performance liquid chromatography
- weight loss
- drug induced
- quantum dots