Favero 2017 Thesis
|Favero BC (2017) Efeitos da leucina sobre a via da mTOR e da miostatina em cultura celular de miotúbulos. Dissertation p55.|
Abstract: Several diseases lead to an unbalance in the metabolic processes, forcing the organism to deplete the body's energetic reserve to supply its own needs. One of these diseases is cachexia, which is present in many patients with cancer. In cachexia, there is an excessive host waste of both adipose and muscle tissues. The tumour mass growing induces the release of many factors which primarily affect the protein metabolism. In this metabolism, the main key protein is mTOR which besides controlling protein synthesis, controls many other events, such as proliferation and cellular differentiation. Thus, the main focus of the present study was reporting the pathways that were affected by mTOR inhibition and how leucine supplementation could modulate these pathways. Leucine is a branched chain amino acid that has been extensively studied due to its effects on protein metabolism, such as enhancing protein synthesis and decreasing protein degradation. C2C12 myoblast cells were differentiated into myotubes and treated with rapamycin to inhibit mTOR's activities. After this, the myotubes were supplemented with leucine to evaluate the signalling pathways modulated by this BCAA and to assess the possible dependence of mTOR in these results. Leucine-treated myotubes increased p70S6K in cells treated with rapamycin. These findings showed that there may be a parallel pathway, independent to mTOR, through which leucine could act in myotubes' protein synthesis. Leucine also decreased Smad2 and inactivated FoxO in myotube cells treated with rapamycin, showing a synergic rapamycin effect. Therefore, leucine increased both oxygen consumption and the cathepsin B activities in C2C12 myotubes, independent of rapamycin inhibition. These results demonstrated that leucine modulated protein metabolism and signalling pathways of energetic metabolism independent of mTOR activation in C2C12 myotubes.
Labels: MiParea: Respiration, mt-Medicine, Pharmacology;toxicology Pathology: Cancer, Other
Organism: Mouse Tissue;cell: Skeletal muscle
Coupling state: LEAK, ROUTINE, ET