Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal muscle
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da USP |
Texto Completo: | https://www.teses.usp.br/teses/disponiveis/109/109131/tde-19092022-073341/ |
Resumo: | Many conditions can induce endoplasmic reticulum (ER) stress, such as inflammation and physical exercise. Toll-like Receptor 4 (TLR4) can trigger inflammation and ER stress events. However, there are still no data in the literature regarding the role of TLR4 in ER stress during exercise in skeletal muscle. Therefore, the current investigation aimed to verify the responses of ER stress markers in wild-type (WT) and Tlr4 global knockout (KO) mice after acute and chronic physical exercise protocols. Eight-week-old male WT and KO mice were submitted to acute (moderate or high intensity) and chronic (4-week protocol) treadmill exercise. Under basal conditions, KO mice showed lower performance in the rotarod test, and increased eIF2α protein phosphorylation compared to WT animals. Acute moderate-intensity exercise increased BiP and CHOP protein in the WT group. After the acute high-intensity exercise, there was an increase in Casp3 and Ddit3 mRNA for the KO mice. Acute exercise increased the cleaved Caspase-3/Caspase-3 in the KO group regardless of exercise intensity. In response to chronic exercise, the KO group showed no improvement in any performance evaluation. The 4-week chronic protocol did not generate changes in CHOP, p-eIF2α/eIF2α, and cleaved Caspase-3/Caspase-3 ratio but reduced BiP protein compared to the KO-Sedentary group. These results demonstrate that the global deletion of Tlr4 seems to protect the mice against ER stress but decreases their performance. The cleaved Caspase-3/Caspase-3 ratio may be activated by another pathway other than ER stress in Tlr4 KO animals. |
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Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal musclePapel do TLR4 no estresse do retículo endoplasmático induzido pelo exercício físico no músculo esqueléticoApoptoseApoptosisExercício físicoKnockout modelModelo NocautePhysical exerciseReceptor tipo TollTLR4TLR4Toll-like receptorMany conditions can induce endoplasmic reticulum (ER) stress, such as inflammation and physical exercise. Toll-like Receptor 4 (TLR4) can trigger inflammation and ER stress events. However, there are still no data in the literature regarding the role of TLR4 in ER stress during exercise in skeletal muscle. Therefore, the current investigation aimed to verify the responses of ER stress markers in wild-type (WT) and Tlr4 global knockout (KO) mice after acute and chronic physical exercise protocols. Eight-week-old male WT and KO mice were submitted to acute (moderate or high intensity) and chronic (4-week protocol) treadmill exercise. Under basal conditions, KO mice showed lower performance in the rotarod test, and increased eIF2α protein phosphorylation compared to WT animals. Acute moderate-intensity exercise increased BiP and CHOP protein in the WT group. After the acute high-intensity exercise, there was an increase in Casp3 and Ddit3 mRNA for the KO mice. Acute exercise increased the cleaved Caspase-3/Caspase-3 in the KO group regardless of exercise intensity. In response to chronic exercise, the KO group showed no improvement in any performance evaluation. The 4-week chronic protocol did not generate changes in CHOP, p-eIF2α/eIF2α, and cleaved Caspase-3/Caspase-3 ratio but reduced BiP protein compared to the KO-Sedentary group. These results demonstrate that the global deletion of Tlr4 seems to protect the mice against ER stress but decreases their performance. The cleaved Caspase-3/Caspase-3 ratio may be activated by another pathway other than ER stress in Tlr4 KO animals.Muitas condições podem induzir o estresse do retículo endoplasmático (RE), como inflamação e exercício físico, por exemplo. O receptor tipo Toll 4 (TLR4) pode desencadear inflamação e eventos de estresse do RE. No entanto, ainda não existem dados na literatura sobre o papel do TLR4 no estresse do RE durante o exercício no músculo esquelético. Portanto, o presente estudo teve como objetivo investigar e verificar as respostas dos marcadores de estresse de RE em camundongos do tipo selvagem (WT) e Tlr4 nocaute global (KO) após protocolos de exercício físico agudo e crônico. Camundongos machos WT e KO com oito semanas de idade foram submetidos a exercícios agudos (moderada ou alta intensidade) e crônicos (protocolo de 4 semanas). Em condições basais, os camundongos KO apresentaram desempenho inferior no teste do rotarod e maior fosforilação da proteína eIF2α em comparação aos animais WT. O exercício agudo de intensidade moderada aumentou a BiP e a proteína CHOP no grupo WT. Após o exercício agudo de alta intensidade, houve aumento nos níveis de RNAm de Casp3 e Ddit3 para os camundongos KO. O exercício agudo aumentou a Caspase-3 clivada/Caspase-3 no grupo KO, independentemente da intensidade do exercício. Em resposta ao exercício crônico, o grupo KO não apresentou melhora em nenhuma avaliação de desempenho. O protocolo crônico de 4 semanas não gerou alterações na CHOP, na razão p-eIF2α/eIF2α e Caspase-3 clivada/Caspase-3, mas reduziu a proteína BiP em relação ao grupo KO-Sedentário. Esses resultados demonstram que a deleção global de Tlr4 parece proteger os camundongos contra o estresse do RE, mas diminui seu desempenho. Ainda, parece que a razão Caspase-3 clivada/Caspase-3 pode ser ativada por outra via diferente do estresse de RE em animais Tlr4 KO.Biblioteca Digitais de Teses e Dissertações da USPSilva, Adelino Sanchez Ramos daMarafon, Bruno Brieda2022-09-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttps://www.teses.usp.br/teses/disponiveis/109/109131/tde-19092022-073341/reponame:Biblioteca Digital de Teses e Dissertações da USPinstname:Universidade de São Paulo (USP)instacron:USPLiberar o conteúdo para acesso público.info:eu-repo/semantics/openAccesseng2022-09-28T12:08:49Zoai:teses.usp.br:tde-19092022-073341Biblioteca Digital de Teses e Dissertaçõeshttp://www.teses.usp.br/PUBhttp://www.teses.usp.br/cgi-bin/mtd2br.plvirginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.bropendoar:27212022-09-28T12:08:49Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal muscle Papel do TLR4 no estresse do retículo endoplasmático induzido pelo exercício físico no músculo esquelético |
title |
Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal muscle |
spellingShingle |
Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal muscle Marafon, Bruno Brieda Apoptose Apoptosis Exercício físico Knockout model Modelo Nocaute Physical exercise Receptor tipo Toll TLR4 TLR4 Toll-like receptor |
title_short |
Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal muscle |
title_full |
Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal muscle |
title_fullStr |
Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal muscle |
title_full_unstemmed |
Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal muscle |
title_sort |
Role of TLR4 in endoplasmic reticulum stress induced by physical exercise in skeletal muscle |
author |
Marafon, Bruno Brieda |
author_facet |
Marafon, Bruno Brieda |
author_role |
author |
dc.contributor.none.fl_str_mv |
Silva, Adelino Sanchez Ramos da |
dc.contributor.author.fl_str_mv |
Marafon, Bruno Brieda |
dc.subject.por.fl_str_mv |
Apoptose Apoptosis Exercício físico Knockout model Modelo Nocaute Physical exercise Receptor tipo Toll TLR4 TLR4 Toll-like receptor |
topic |
Apoptose Apoptosis Exercício físico Knockout model Modelo Nocaute Physical exercise Receptor tipo Toll TLR4 TLR4 Toll-like receptor |
description |
Many conditions can induce endoplasmic reticulum (ER) stress, such as inflammation and physical exercise. Toll-like Receptor 4 (TLR4) can trigger inflammation and ER stress events. However, there are still no data in the literature regarding the role of TLR4 in ER stress during exercise in skeletal muscle. Therefore, the current investigation aimed to verify the responses of ER stress markers in wild-type (WT) and Tlr4 global knockout (KO) mice after acute and chronic physical exercise protocols. Eight-week-old male WT and KO mice were submitted to acute (moderate or high intensity) and chronic (4-week protocol) treadmill exercise. Under basal conditions, KO mice showed lower performance in the rotarod test, and increased eIF2α protein phosphorylation compared to WT animals. Acute moderate-intensity exercise increased BiP and CHOP protein in the WT group. After the acute high-intensity exercise, there was an increase in Casp3 and Ddit3 mRNA for the KO mice. Acute exercise increased the cleaved Caspase-3/Caspase-3 in the KO group regardless of exercise intensity. In response to chronic exercise, the KO group showed no improvement in any performance evaluation. The 4-week chronic protocol did not generate changes in CHOP, p-eIF2α/eIF2α, and cleaved Caspase-3/Caspase-3 ratio but reduced BiP protein compared to the KO-Sedentary group. These results demonstrate that the global deletion of Tlr4 seems to protect the mice against ER stress but decreases their performance. The cleaved Caspase-3/Caspase-3 ratio may be activated by another pathway other than ER stress in Tlr4 KO animals. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-09-12 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.teses.usp.br/teses/disponiveis/109/109131/tde-19092022-073341/ |
url |
https://www.teses.usp.br/teses/disponiveis/109/109131/tde-19092022-073341/ |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
|
dc.rights.driver.fl_str_mv |
Liberar o conteúdo para acesso público. info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Liberar o conteúdo para acesso público. |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.coverage.none.fl_str_mv |
|
dc.publisher.none.fl_str_mv |
Biblioteca Digitais de Teses e Dissertações da USP |
publisher.none.fl_str_mv |
Biblioteca Digitais de Teses e Dissertações da USP |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da USP instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Biblioteca Digital de Teses e Dissertações da USP |
collection |
Biblioteca Digital de Teses e Dissertações da USP |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
virginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.br |
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1809090870751789056 |