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Master's Dissertation
DOI
https://doi.org/10.11606/D.109.2022.tde-23032022-093425
Document
Author
Full name
Rafael Lemes Rovina
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2022
Supervisor
Committee
Silva, Adelino Sanchez Ramos da (President)
Pauli, Jose Rodrigo
Santiago, Paulo Roberto Pereira
Title in Portuguese
Papel da interleucina-6 nas respostas da via da autofagia no coração de camundongos submetidos ao exercício físico agudo exaustivo
Keywords in Portuguese
Autofagia
Exercício físico
Interleucina-6
Músculo cardíaco
Abstract in Portuguese
O desequilíbrio entre o excesso de exercício físico e o período adequado de recuperação está associado com sinais de hipertrofia cardíaca patológica, diminuição da fosforilação da proteína AMP-activated protein kinase (AMPK) no resíduo tirosina 172, e aumento das concentrações de interleucina-6 (IL6) no soro e tecido cardíaco de camundongos. Sabe-se que o aumento da IL6 é capaz de inibir o processo de autofagia, cuja ativação é considerada um alvo terapêutico promissor para a prevenção e o tratamento de doenças cardiovasculares. Nesse sentido, o objetivo foi investigar o papel da IL6 nas respostas da via da autofagia no coração de camundongos submetidos ao exercício físico agudo exaustivo. Para tanto, camundongos wild-type C57BL/6J (WT) e knockout de IL6 (IL6KO) foram submetidos a um protocolo de exercício físico agudo exaustivo. Amostras de soro e do músculo cardíaco foram coletadas no tempo basal, 1h e 3h após o protocolo de exercício físico exaustivo. Os parâmetros funcionais, séricos e moleculares foram analisados pelo ecocardiograma, fluxo autofágico, além das técnicas de Real time-RTqPCR e immunoblotting. De acordo com a distribuição estatística dos dados, foram utilizados testes paramétricos ou não paramétricos para a análise dos resultados, sendo adotado o nível de significância de p≤0, 05. Foi observado nos camundongos knockout de IL6, menor tolerância ao exercício físico (p=0,003), maior consumo de oxigênio no estado basal (p=0,001), e três horas após a sessão de exercício os níveis de mRNA de Mtco1, Mtnd1 e Nampt foram menores (p=0,001; p=0,002; p=0,005). Portanto, a IL6 parece ter importante papel no desempenho físico e consumo de oxigênio, porém não foi observado nenhuma alteração no fluxo autofágico em resposta ao exercício.
Title in English
Role of interleukin-6 in the responses of the autophagy pathway in the heart of mice submitted to exhaustive acute physical exercise
Keywords in English
Autophagy
Cardiac muscle
Interleukin-6
Physical exercise
Abstract in English
The imbalance between excess physical exercise and the appropriate recovery period is associated with signs of pathological cardiac hypertrophy, decreased phosphorylation of Amp-activated protein kinase (AMPK) protein in tyrosine residue 172, and increased concentrations of interleukin-6 (IL6) in serum and cardiac tissue of mice. It is known that the increase in IL6 is capable of inhibiting the process of autophagy, whose activation is considered a promising therapeutic target for the prevention and treatment of cardiovascular diseases. In this sense, the main objective of this research project will be to investigate the role of IL6 in the responses of the autophagy pathway in the heart of mice submitted to exhaustive acute physical exercise. For this, wild-type mice C57BL/6J (WT) and IL6 knockout (KO) will undergo an exhaustive acute exercise protocol. Serum and heart muscle samples will be collected immediately, 1h and 3h after the exhaustive exercise protocol. The functional, seric and molecular parameters will be analyzed by echocardiogram, autophagic flow, in addition to the techniques of Real time-RTqPCR (Reverse Transcription Polymerase Chain Reaction) and immunoblotting. According to the statistical distribution of the data, parametric or nonparametric tests will be used for the analysis of the results. The significance level of p≤0, 05 will be adopted. In IL6 knockout mice, we observed lower exercise tolerance (p=0.003), higher oxygen consumption at baseline (p=0.001), and three hours after the exercise session Mtco1, Mtnd1 and Nampt mRNA levels were lower (p=0.001; p=0.002; p=0.005). Therefore, IL6 appears to play an important role in physical performance and oxygen consumption, but no change in autophagic flux was observed in response to exercise.
 
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Publishing Date
2022-04-14
 
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