IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3389/fimmu.2022.953272 http://hdl.handle.net/11449/247822 |
Resumo: | Interleukin 6 (IL-6) acts as a pro and anti-inflammatory cytokine, has an intense correlation with exercise intensity, and activates various pathways such as autophagy and mitochondrial unfolded protein response. Also, IL-6 is interconnected to circadian clock-related inflammation and can be suppressed by the nuclear receptor subfamily 1, group D, member 1 (Nr1d1, protein product REV-ERBα). Since IL-6 is linked to physical exercise-modulated metabolic pathways such as autophagy and mitochondrial metabolism, we investigated the relationship of IL-6 with REV-ERBα in the adaptations of these molecular pathways in response to acute intense physical exercise in skeletal muscle. The present study was divided into three experiments. In the first one, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were divided into three groups: Basal time (Basal; sacrificed before the acute exercise), 1 hour (1hr post-Ex; sacrificed 1 hour after the acute exercise), and 3 hours (3hr post-Ex; sacrificed 3 hours after the acute exercise). In the second experiment, C2C12 cells received IL-6 physiological concentrations or REV-ERBα agonist, SR9009. In the last experiment, WT mice received SR9009 injections. After the protocols, the gastrocnemius muscle or the cells were collected for reverse transcription-quantitative polymerase chain reaction (RTq-PCR) and immunoblotting techniques. In summary, the downregulation of REV-ERBα, autophagic flux, and most mitochondrial genes was verified in the IL-6 KO mice independent of exercise. The WT and IL-6 KO treated with SR9009 showed an upregulation of autophagic genes. C2C12 cells receiving IL-6 did not modulate the Nr1d1 mRNA levels but upregulated the expression of some mitochondrial genes. However, when treated with SR9009, IL-6 and mitochondrial gene expression were upregulated in C2C12 cells. The autophagic flux in C2C12 suggest the participation of REV-ERBα protein in the IL-6-induced autophagy. In conclusion, the present study verified that the adaptations required through physical exercise (increases in mitochondrial content and improvement of autophagy machinery) might be intermediated by an interaction between IL-6 and REVERBα. |
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IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exerciseautophagic fluxC2C12 cellsgenetic deletionmitochondriaNr1d1pharmacological treatmentInterleukin 6 (IL-6) acts as a pro and anti-inflammatory cytokine, has an intense correlation with exercise intensity, and activates various pathways such as autophagy and mitochondrial unfolded protein response. Also, IL-6 is interconnected to circadian clock-related inflammation and can be suppressed by the nuclear receptor subfamily 1, group D, member 1 (Nr1d1, protein product REV-ERBα). Since IL-6 is linked to physical exercise-modulated metabolic pathways such as autophagy and mitochondrial metabolism, we investigated the relationship of IL-6 with REV-ERBα in the adaptations of these molecular pathways in response to acute intense physical exercise in skeletal muscle. The present study was divided into three experiments. In the first one, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were divided into three groups: Basal time (Basal; sacrificed before the acute exercise), 1 hour (1hr post-Ex; sacrificed 1 hour after the acute exercise), and 3 hours (3hr post-Ex; sacrificed 3 hours after the acute exercise). In the second experiment, C2C12 cells received IL-6 physiological concentrations or REV-ERBα agonist, SR9009. In the last experiment, WT mice received SR9009 injections. After the protocols, the gastrocnemius muscle or the cells were collected for reverse transcription-quantitative polymerase chain reaction (RTq-PCR) and immunoblotting techniques. In summary, the downregulation of REV-ERBα, autophagic flux, and most mitochondrial genes was verified in the IL-6 KO mice independent of exercise. The WT and IL-6 KO treated with SR9009 showed an upregulation of autophagic genes. C2C12 cells receiving IL-6 did not modulate the Nr1d1 mRNA levels but upregulated the expression of some mitochondrial genes. However, when treated with SR9009, IL-6 and mitochondrial gene expression were upregulated in C2C12 cells. The autophagic flux in C2C12 suggest the participation of REV-ERBα protein in the IL-6-induced autophagy. In conclusion, the present study verified that the adaptations required through physical exercise (increases in mitochondrial content and improvement of autophagy machinery) might be intermediated by an interaction between IL-6 and REVERBα.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)School of Physical Education and Sport of Ribeirão Preto University of São Paulo (USP)Postgraduate Program in Rehabilitation and Functional Performance Ribeirão Preto Medical School University of São Paulo (USP)Department of Biomolecular Sciences School of Pharmaceutical Sciences of Ribeirao Preto Faculty of Pharmaceutical Sciences of Ribeirao Preto University of São Paulo (FCFRP USP)Laboratory of Molecular Biology of Exercise (LaBMEx) School of Applied Sciences University of Campinas (UNICAMP)Department of Biochemistry Federal University of São Paulo (UNIFESP)Multicentric Program of Postgraduate in Physiological Sciences School of Dentistry of Araçatuba São Paulo State University (UNESP)Department of Physical Education State University of São Paulo (UNESP)Multicentric Program of Postgraduate in Physiological Sciences School of Dentistry of Araçatuba São Paulo State University (UNESP)Department of Physical Education State University of São Paulo (UNESP)FAPESP: 2017/12765-2FAPESP: 2018/14818-9FAPESP: 2019/11820-5FAPESP: 2019/21709-4FAPESP: 2020/13443-1FAPESP: 2021/08692-5FAPESP: 2021/08693-1Universidade de São Paulo (USP)Universidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (UNESP)Pinto, Ana P.Muñoz, Vitor R.da Rocha, Alisson L.Rovina, Rafael L.Ferrari, Gustavo D.Alberici, Luciane C.Simabuco, Fernando M.Teixeira, Giovana R. [UNESP]Pauli, José R.de Moura, Leandro P.Cintra, Dennys E.Ropelle, Eduardo R.Freitas, Ellen C.Rivas, Donato A. [UNESP]da Silva, Adelino S. R.2023-07-29T13:26:47Z2023-07-29T13:26:47Z2022-10-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fimmu.2022.953272Frontiers in Immunology, v. 13.1664-3224http://hdl.handle.net/11449/24782210.3389/fimmu.2022.9532722-s2.0-85141003951Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Immunologyinfo:eu-repo/semantics/openAccess2023-07-29T13:26:47Zoai:repositorio.unesp.br:11449/247822Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-07-29T13:26:47Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise |
title |
IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise |
spellingShingle |
IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise Pinto, Ana P. autophagic flux C2C12 cells genetic deletion mitochondria Nr1d1 pharmacological treatment |
title_short |
IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise |
title_full |
IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise |
title_fullStr |
IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise |
title_full_unstemmed |
IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise |
title_sort |
IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise |
author |
Pinto, Ana P. |
author_facet |
Pinto, Ana P. Muñoz, Vitor R. da Rocha, Alisson L. Rovina, Rafael L. Ferrari, Gustavo D. Alberici, Luciane C. Simabuco, Fernando M. Teixeira, Giovana R. [UNESP] Pauli, José R. de Moura, Leandro P. Cintra, Dennys E. Ropelle, Eduardo R. Freitas, Ellen C. Rivas, Donato A. [UNESP] da Silva, Adelino S. R. |
author_role |
author |
author2 |
Muñoz, Vitor R. da Rocha, Alisson L. Rovina, Rafael L. Ferrari, Gustavo D. Alberici, Luciane C. Simabuco, Fernando M. Teixeira, Giovana R. [UNESP] Pauli, José R. de Moura, Leandro P. Cintra, Dennys E. Ropelle, Eduardo R. Freitas, Ellen C. Rivas, Donato A. [UNESP] da Silva, Adelino S. R. |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual de Campinas (UNICAMP) Universidade Estadual Paulista (UNESP) |
dc.contributor.author.fl_str_mv |
Pinto, Ana P. Muñoz, Vitor R. da Rocha, Alisson L. Rovina, Rafael L. Ferrari, Gustavo D. Alberici, Luciane C. Simabuco, Fernando M. Teixeira, Giovana R. [UNESP] Pauli, José R. de Moura, Leandro P. Cintra, Dennys E. Ropelle, Eduardo R. Freitas, Ellen C. Rivas, Donato A. [UNESP] da Silva, Adelino S. R. |
dc.subject.por.fl_str_mv |
autophagic flux C2C12 cells genetic deletion mitochondria Nr1d1 pharmacological treatment |
topic |
autophagic flux C2C12 cells genetic deletion mitochondria Nr1d1 pharmacological treatment |
description |
Interleukin 6 (IL-6) acts as a pro and anti-inflammatory cytokine, has an intense correlation with exercise intensity, and activates various pathways such as autophagy and mitochondrial unfolded protein response. Also, IL-6 is interconnected to circadian clock-related inflammation and can be suppressed by the nuclear receptor subfamily 1, group D, member 1 (Nr1d1, protein product REV-ERBα). Since IL-6 is linked to physical exercise-modulated metabolic pathways such as autophagy and mitochondrial metabolism, we investigated the relationship of IL-6 with REV-ERBα in the adaptations of these molecular pathways in response to acute intense physical exercise in skeletal muscle. The present study was divided into three experiments. In the first one, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were divided into three groups: Basal time (Basal; sacrificed before the acute exercise), 1 hour (1hr post-Ex; sacrificed 1 hour after the acute exercise), and 3 hours (3hr post-Ex; sacrificed 3 hours after the acute exercise). In the second experiment, C2C12 cells received IL-6 physiological concentrations or REV-ERBα agonist, SR9009. In the last experiment, WT mice received SR9009 injections. After the protocols, the gastrocnemius muscle or the cells were collected for reverse transcription-quantitative polymerase chain reaction (RTq-PCR) and immunoblotting techniques. In summary, the downregulation of REV-ERBα, autophagic flux, and most mitochondrial genes was verified in the IL-6 KO mice independent of exercise. The WT and IL-6 KO treated with SR9009 showed an upregulation of autophagic genes. C2C12 cells receiving IL-6 did not modulate the Nr1d1 mRNA levels but upregulated the expression of some mitochondrial genes. However, when treated with SR9009, IL-6 and mitochondrial gene expression were upregulated in C2C12 cells. The autophagic flux in C2C12 suggest the participation of REV-ERBα protein in the IL-6-induced autophagy. In conclusion, the present study verified that the adaptations required through physical exercise (increases in mitochondrial content and improvement of autophagy machinery) might be intermediated by an interaction between IL-6 and REVERBα. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-10-13 2023-07-29T13:26:47Z 2023-07-29T13:26:47Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/fimmu.2022.953272 Frontiers in Immunology, v. 13. 1664-3224 http://hdl.handle.net/11449/247822 10.3389/fimmu.2022.953272 2-s2.0-85141003951 |
url |
http://dx.doi.org/10.3389/fimmu.2022.953272 http://hdl.handle.net/11449/247822 |
identifier_str_mv |
Frontiers in Immunology, v. 13. 1664-3224 10.3389/fimmu.2022.953272 2-s2.0-85141003951 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers in Immunology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799964515727572992 |