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Potential of targeting protein breakdown mechanism (specific E3 ubiquitin ligases) in vitro and in vivo models of cachexia/muscle atrophy

Grant number: 17/20288-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): January 08, 2018
Effective date (End): December 21, 2018
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Maria Cristina Cintra Gomes Marcondes
Grantee:Laís Rosa Viana
Supervisor abroad: Paul Gregorevic
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: Baker IDI Heart & Diabetes Institute, Australia  
Associated to the scholarship:15/21890-0 - Effect of leucine, ketogenic and combined diets in tumor growth, cachectic state and metabolomic systemic profile, muscle and tumor in rats with cancer cachexia (Walker 256 model), BP.PD

Abstract

Cachexia is a multi-factorial syndrome that affects up to 80% of cancer patients and is significantly related to decrement of quality of life and cancer deaths. Skeletal muscle wasting is the main consequence of cachexia and largely contributes to involuntary weight loss. This skeletal muscle wasting is a result of an increase in protein breakdown and decrease in protein synthesis. Protein breakdown mechanism is stimulated by some tumour delivered factors, such as proteolysis-inducing factor (PIF) and pro-inflammatory cytokines including tumor necrosis factor-± (TNF-±). The major protein breakdown pathway is the ubiquitin-proteasome proteolytic system that involves the protein ubiquitination cascade. E3 ligases carry out the final step in the ubiquitination cascade, being essential for this catalytic mechanism. Targeting E3 ligases would allow efficacy therapies for cachexia/muscle atrophy. Therefore, the aim of this project is to evaluate the effects of targeting protein breakdown mechanisms (specific E3 ubiquitin ligases) in in vitro and in vivo models of cachexia. C2C12 murine myoblast cells and BALB/c mice inoculated with C26 colon carcinoma tumor (experimental model of cancer cachexia) will be used to evaluate the effects of targeting E3 ligases in skeletal muscle degradation pathway.

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