Rapid changes in transcriptomic profile and mitochondrial function in human soleus muscle after three-day dry immersion

We aimed to explore the effect of the 3-day dry immersion - a model of physical unloading - on mitochondrial function, transcriptomic and proteomic profiles in a slow-twitch m. soleus of six healthy females. We registered that a marked reduction (25-34%) in the ADP-stimulated respiration in permeabilized muscle fibers was not accompanied by a decrease in the content of mitochondrial enzymes (mass spectrometry-based quantitative proteomics), hence it is related to the disruption in regulation of respiration. We detected a widespread change in the transcriptomic profile (RNA-seq) upon dry immersion. Down-regulated mRNAs were strongly associated with mitochondrial function, as well as with lipid metabolism, glycolysis, insulin signaling, and various transporters. Despite the substantial transcriptomic response, we found no effect on the content of highly abundant proteins (sarcomeric, mitochondrial, chaperon and extracellular matrix-related, etc.) that may be explained by long half-life of these proteins. We suggest that during short-term disuse the content of some regulatory (and usually low abundant) proteins such as cytokines, receptors, transporters, transcription regulators is largely determined by its mRNA concentration. These mRNAs revealed in our work may serve as putative targets for the future studies aimed at developing the approaches for the prevention of muscle deconditioning-induced by disuse. Overall design: Six healthy females (25-39 years old [range]; median height 1.64 m and interquartile range [1.62-1.70] m; body mass 64.9 [60.8-67.9] kg; BMI 22.39 [20.19-24.59] kg/m2) were exposed to 3 days of “dry” immersion. Samples from the soleus muscle were taken prior to and after “dry” immersion from the left leg using a modified Bergström biopsy needle with manual suction under local anesthesia (2 ml 2% lidocaine). Both biopsies were taken on the 10-th day of the menstrual cycle. Strand-specific libraries were prepared and sequenced (75 nucleotides, single end) by NextSeq 550 (Illumina, USA).