IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise.

Autor:	Pinto AP; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), São Paulo, Brazil., Muñoz VR; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), São Paulo, Brazil., da Rocha AL; Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), São Paulo, Brazil., Rovina RL; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), São Paulo, Brazil., Ferrari GD; Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, Faculty of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo (FCFRP USP), Sao Paulo, Brazil., Alberici LC; Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, Faculty of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo (FCFRP USP), Sao Paulo, Brazil., Simabuco FM; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), São Paulo, Brazil.; Department of Biochemistry, Federal University of São Paulo (UNIFESP), São Paulo, Brazil., Teixeira GR; Multicentric Program of Postgraduate in Physiological Sciences, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil.; Department of Physical Education, State University of São Paulo (UNESP), São Paulo, Brazil., Pauli JR; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), São Paulo, Brazil., de Moura LP; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), São Paulo, Brazil., Cintra DE; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), São Paulo, Brazil., Ropelle ER; Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), São Paulo, Brazil., Freitas EC; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), São Paulo, Brazil., Rivas DA; Multicentric Program of Postgraduate in Physiological Sciences, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil., da Silva ASR; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), São Paulo, Brazil.; Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Oct 13; Vol. 13, pp. 953272. Date of Electronic Publication: 2022 Oct 13 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.953272
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Pinto, Muñoz, da Rocha, Rovina, Ferrari, Alberici, Simabuco, Teixeira, Pauli, de Moura, Cintra, Ropelle, Freitas, Rivas and da Silva.)
Databáze:	MEDLINE
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