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Protein quality control profile in skeletal muscle wasting: role of beta2- adrenergic receptor

Grant number: 12/14416-1
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2012
Effective date (End): 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


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. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CAMPOS, JULIANE C.; BAEHR, LESLIE M.; FERREIRA, NIKOLAS D.; BOZI, LUIZ H. M.; ANDRES, ALLEN M.; RIBEIRO, MARCIO A. C.; GOTTLIEB, ROBERTA A.; BODINE, SUE C.; FERREIRA, JULIO C. B.. beta(2)-adrenoceptor activation improves skeletal muscle autophagy in neurogenic myopathy. FASEB JOURNAL, v. 34, n. 4, . (18/18627-3, 16/01633-5, 17/16540-5, 12/14416-1, 15/50429-9, 17/16694-2)
CAMPOS, JULIANE C.; BAEHR, LESLIE M.; GOMES, KATIA M. S.; BECHARA, LUIZ R. G.; VOLTARELLI, VANESSA A.; BOZI, LUIZ H. M.; RIBEIRO, MARCIO A. C.; FERREIRA, NIKOLAS D.; MOREIRA, JOSE B. N.; BRUM, PATRICIA C.; et al. Exercise prevents impaired autophagy and proteostasis in a model of neurogenic myopathy. SCIENTIFIC REPORTS, v. 8, . (12/14416-1, 16/01633-5, 15/22814-5, 15/20783-5)
CAMPOS, JULIANE C.; BOZI, LUIZ H. M.; BECHARA, LUIZ R. G.; LIMA, VANESSA M.; FERREIRA, JULIO C. B.. Mitochondrial Quality Control in Cardiac Diseases. FRONTIERS IN PHYSIOLOGY, v. 7, . (12/19379-7, 12/14416-1, 15/20783-5, 12/05765-2, 16/01633-5)
BOZI, LUIZ H. M.; CAMPOS, JULIANE C.. Targeting the ubiquitin proteasome system in diabetic cardiomyopathy. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, v. 109, p. 61-63, . (12/14416-1, 16/09611-0)
CAMPOS, JULIANE C.; GOMES, KATIA M. S.; FERREIRA, JULIO C. B.. Impact of exercise training on redox signaling in cardiovascular diseases. Food and Chemical Toxicology, v. 62, p. 107-119, . (12/05765-2, 12/14416-1)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CAMPOS, Juliane Cruz. Protein quality control in skeletal muscle weakness/wasting: role of β2-adrenoceptor.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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