ROLE OF AMP-ACTIVATED PROTEIN KINASE IN REGULATION OF CALCIUM-DEPENDENT AND UBIQUITIN/PROTEASOME SIGNALING PATHWAYS DURING MUSCLE FUNCTIONAL DISLOADING

Abstract

We tested the hypothesis that in unloaded skeletal muscles the calcium-dependent signaling pathways and E3-ligase expression are controlled by regulation of phosphorylation of AMP-activated protein kinase (AMPK). For a 3-d experiment 32 Wister male rats were divided into 4 groups: placebo control (С), metformin control (300 mg/kg of body, per oral, MC), suspension and placebo (SP), suspension and metformin (SM). Object of the investigation was m. soleus. In comparison to group C, rAMPK in group MC reduced 46 % and ATP increased 49 % (p < 0.05); pCaMK II showed an increase and expression of mRNA CaN, SERCA2a and Calpain 1 grew 483 %, 87 %, 41 % and 62 %, respectively; p < 0.05). In group SP, MuRF1, MAFbx E3-ligase expression and ubiquitin increased 167 %, 146 % and 191 %, respectively (p < 0.05). Per oral metformin prevented these changes in the suspended rats. During 3 days of suspension, metformin prevented changes in rAMK and ATP; also, it influenced regulation of the calcium-dependent signaling pathways through expression and phosphorylation of such markers as CaMK, CaN, SERCA2a and Calpain-1, and prevented to a degree growth in expression of key markers of ubuquitin-proteasome pathway – MuRF1, MAFbx, and uniquitin.