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Master's Dissertation
DOI
10.11606/D.39.2010.tde-18082010-150129
Document
Author
Full name
Telma Fátima da Cunha
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Brum, Patricia Chakur (President)
Navegantes, Luiz Carlos Carvalho
Tinucci, Tais
Title in Portuguese
Efeito do treinamento físico aeróbico sobre a atrofia muscular associada à insuficiência cardíaca: contribuição do sistema ubiquitina proteassoma dependente de ATP
Keywords in Portuguese
Hiperatividade simpática
Infarto do miocárdio
Insuficiência cardíaca
Sistema ubiquitina proteassoma
Treinamento físico aeróbico
Abstract in Portuguese
A atrofia está associada ao aumento da degradação protéica em doenças sistêmicas, sendo o sistema proteolítico ubiquitina proteassoma (SUP) uma das principais vias envolvidas. Contudo, pouco é conhecido sobre a contribuição do SUP à atrofia desencadeada pela insuficiência cardíaca (IC). Sabendo dos benefícios do treinamento físico aeróbico (TFA) e que os mecanismos moleculares envolvidos na atrofia na IC ainda não estão esclarecidos, nessa dissertação investigamos: 1) a contribuição do SUP para a atrofia associada à IC em 2 modelos experimentais: um modelo genético de camundongos com hiperatividade simpática (HS), e um modelo de infarto do miocárdio (IM) em ratos e 2) o efeito do TFA sobre a atrofia associada à IC e sobre o SUP. Na HS verificamos aumento da expressão das E3 ligases, da deubiquitinase USP28, das proteínas ubiquitinadas e da atividade do proteassoma no sítio quimiotripsina, sendo que o TFA reduziu a expressão dos componentes alterados. No IM, observamos disfunção cardíaca não associada à IC, porém, com aumento da expressão de Atrogin-1; enquanto o TFA não produziu efeitos significantes. Dessa forma, os dados sugerem a participação do SUP na atrofia desencadeada pela IC na HS e, que o TFA previne a atrofia por reduzir a expressão/atividade de alguns componentes do SUP; e, que no IM, o aumento da expressão de Atrogin-1 precedeu a perda de massa muscular
Title in English
Effects of aerobic exercise training on skeletal muscle atrophy associated with heart failure: role of ubiquitin-proteasome pathway
Keywords in English
Endurance exercise training
Heart failure
Ischemia
Sympathetic hyperactivity
Ubiquitin-proteasome pathway
Abstract in English
Skeletal muscle atrophy is associated with increased protein degradation in systemic diseases, which seems to be mainly related to ubiquitin-proteasome system (UPS). However, little is known about UPS contribution to the heart failure-induced muscle atrophy (HF-MA). Likewise, aerobic exercise training (AET) has been established as an adjuvant therapy for HF and molecular mechanisms underlying HF-MA has not been clarified yet. The objectives of the study were: 1) to verify UPS contribution for HF-MA in 2 experimental models: sympathetic hyperactivity-induced HF (α2A2CARKO) in mice, and myocardial infarction model (MI) in rats and 2) AET effects on HF-MA and UPS. In α2A2C ARKO mice, we observed activation of UPS characterized by increased mRNA levels of E3 ligases Atrogin-1 and E3-a, deubiquitinating enzyme USP28, increased levels of ubiquitinated proteins and chymotrypsin-like proteasome activity. AET prevented HF-MA in the α2A2C ARKO by reducing of UPS activity. In MI model, rats displayed cardiac dysfunction and exercise intolerance with no signs of atrophy. However, Atrogin-1 mRNA and protein levels were increased. Therefore, alterations in Atrogin-1expression might precede atrophy and HF in this model. In conclusion, our data provide evidence for skeletal muscle anti-atrophic effect upon AET in α2A2C ARKO that is related, at least in part, to a reduced UPS
 
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4_Telma_Sumario.pdf (43.06 Kbytes)
Publishing Date
2011-05-27
 
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