| Grant number: | 12/14416-1 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | November 01, 2012 |
| End date: | July 31, 2017 |
| Field of knowledge: | Biological Sciences - Physiology - Physiology of Organs and Systems |
| Principal Investigator: | Julio Cesar Batista Ferreira |
| Grantee: | Juliane Cruz Campos |
| Host Institution: | Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated scholarship(s): | 16/01633-5 - BETA2-ADRENOCEPTOR ACTIVATION COUNTERACTS SKELETAL MUSCLE WEAKNESS/WASTING: ROLE OF AUTOPHAGY, BE.EP.DR |
Abstract Skeletal muscle weakness and wasting are common features of many degenerative diseases, including cancer, sepsis and cardiovascular diseases. The clinical consequences of muscle wasting/weakness include elevated morbidity and mortality. Muscle atrophy has been related to increased oxidative stress and consequent impairment of protein quality control (PQC).The PQC components, including ubiquitin proteasome system (UPS), lysosomes, and chaperones, play important role in monitoring and protecting long lived-cells against the accumulation of damaged proteins. We propose here to better understand the profile of PQC during the progression of muscle atrophy/dysfunction. Our preliminary data show increased UPS proteolytic activity followed by accumulation of damaged proteins in atrophic skeletal muscles due to sciatic nerve constriction (CSC) in rats. These results suggest a disruption of PQC in CSC animal model. After characterizing the PQC profile, we intend to investigate the role of the main PQC component (UPS) in skeletal muscle atrophy/dysfunction by using activators and inhibitors of SUP. Finally, we plan to validate our in vivo findings using myoblasts in culture.Considering the clinical relevance of skeletal muscle weakness/wasting, a detailed understanding of myocyte PQC is required. Moreover, clarifying the modulation of PQC components as well as their intermolecular interactions will be crucial for future therapy strategies to counteract skeletal muscle illness. | |
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