Effect of β-GPA on the Anabolic and Catabolic Markers in Rat Soleus Muscle at the Initial Stage of Gravitational Unloading

Molecular mechanisms initiating the development of atrophic changes in a mammalian postural muscle remain unclear. Since skeletal muscle inactivation can lead to changes in the balance of intramuscular high-energy phosphates, we suggested that AMP-activated protein kinase (AMPK) may play an important role in the regulation of anabolic and catabolic signaling pathways in postural muscle at the initial stage of mechanical unloading. Beta-guanidinopropionic acid (beta-GPA) can act as a modulator of the balance of macroergic compounds, which can reduce the content of intracellular high-energy phosphates. The purpose of the study was to assess signaling pathways of protein synthesis and degradation in rat soleus muscle after preliminary treatment with beta-GPA followed by 1-day hindlimb unloading. Male Wistar rats that were divided into the following groups: 1) vivarium control (C); 2) vivarium control + beta-GPA (C+GPA); 3) 1-day hindlimb unloading (HU); 4) 1-day HU + beta-GPA (HU+GPA). beta-GPA was administered daily by intraperitoneal injections (400 mg/kg). The content of the key signaling proteins (AMPK, ACC, p70S6K, 4E-BP1, FOXO3) was determined by gel electrophoresis followed by immunoblotting. mRNA expression of ubiquitin ligases (MuRF-1 and MAFbx) was evaluated using real-time PCR. In the group with 1-day unloading and beta-GPA pretreatment, a prevention of reduction in phosphorylation of AMPK, ACC and 4E-BP1 was observed, and the increased level of p70S6K phosphorylation returned to control values. The phosphorylation of AKT and FOXO3, as well as the expression level of MuRF-1 and MAFbx in the HU + GPA group did not differ from the HU group. To conclude, the AMPK activity may play an important role in the modulation of anabolic mTORC1-signaling in rat soleus muscle at the early stage of simulated microgravity.