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Mémoire de Maîtrise
DOI
10.11606/D.17.2017.tde-04012017-113714
Document
Auteur
Nom complet
Adriana Caldo Silva
Adresse Mail
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
Ribeirão Preto, 2016
Directeur
Jury
Silva, Adelino Sanchez Ramos da (Président)
Pauli, Jose Rodrigo
Puggina, Enrico Fuini
Titre en portugais
Efeitos do overreaching não funcional sobre a via da mTOR no tecido hepático de camundongos
Mots-clés en portugais
Fígado
mTOR
Overreaching não funcional
Overtraining
Resumé en portugais
O propósito do presente estudo foi verificar os efeitos do overtraining (OT) nas proteínas relacionadas com a via de sinalização da mammalian target of the rapamycin complex 1 (mTORC1), no conteúdo proteico de sterol regulatory element binding protein-1 (SREBP-1) e nas características morfológicas do fígado de camundongos C57BL/6. Os animais foram divididos em grupo controle (CT), overtraining em declive (OTR/down), overtraining em aclive (OTR/up) e overtraining sem inclinação (OTR). Teste do rotarod, incremental, exaustivo e força de preensão foram utilizados para avaliação de performance. Após 36 horas o teste de força de preensão, os fígados foram removidos e utilizados para immunoblotting ou análises histológicas. A fosforilação da proteína kinase B (pAkt; Ser473), mammalian target of the rapamycin (pmTOR; Ser2448), 70-kDa ribosomal protein S6 kinase 1 (pS6K1; Thr389) e da AMP-activated protein kinase (pAMPK; Thr172) foram significativamente maiores no grupo OTR/down quando comparado com os grupos CT e OTR. A fosforilação da 4E-binding protein-1 (p4E-BP1; Thr37/46) foi significativamente maior no grupo OTR/down quando comparado com o grupo CT. Os níveis proteicos de sterol regulatory element binding protein- 1 (SREBP-1; p125 precursor) foram significativamente maiores nos grupos OTR/down e OTR/up quando comparados com o grupo CT. Enquanto o grupo OTR/down apresentou sinais de esteatose com inchaço celular acompanhado de inflamação aguda, os grupos OTR/up e OTR demonstraram evidências de injúria hepática, com a presença de núcleos picnóticos, hepatócitos em balão e vacúolos citoplasmáticos. Conclui-se que o protocolo de OTR/down aumenta a modulação da via de sinalização da mTOR e induz a sinais de esteatose hepática.
Titre en anglais
Effects of nonfunctional overreaching of the mTOR pathway in hepatic tissue of mice
Mots-clés en anglais
Liver
mTOR
Nonfunctional overreaching
Overtraining
Resumé en anglais
The purpose of this study was to verify the effects of overtraining (OT) on the proteins related to the mammalian target of the rapamycin complex 1 (mTORC1) signaling pathway, the protein content of the sterol regulatory element binding protein-1 (SREBP-1) and the morphological characteristics in the livers of C57BL/6 mice. Rodents were divided into control (CT), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR) groups. Rotarod, incremental load, exhaustive and grip force tests were used to evaluate performance. Thirty-six hours after the grip force test, the livers were removed and used for immunoblotting or histological analysis. The phosphorylation of the protein kinase B (pAkt; Ser473), mammalian target of the rapamycin (pmTOR; Ser2448), 70-kDa ribosomal protein S6 kinase 1 (pS6K1; Thr389) and AMP-activated protein kinase (pAMPK; Thr172) were significantly higher in the OTR/down group when compared to the CT and OTR groups. The phosphorylation of the 4Ebinding protein-1 (p4E-BP1; Thr37/46) was significantly higher in the OTR/down group when compared to the CT group. The protein levels of the sterol regulatory element binding protein-1 (SREBP-1; p125 precursor) were significantly higher in the OTR/down and OTR/up groups when compared to the CT group. While the OTR/down group presented signs of steatosis with cell swelling accompanied by acute inflammation, the OTR/up and OTR groups demonstrated evidences of injury in liver, with the presence of pyknotic nuclei, ballooned hepatocytes and cytoplasmic vacuoles. In conclusion, the OTR/down protocol up-modulated the mTOR signaling pathway and induced signs of hepatic steatosis.
 
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Date de Publication
2017-04-13
 
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