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Quantitative Proteomics Identifies Novel Nrf2-Mediated Adaptative Signaling Pathways in Skeletal Muscle Following Exercise Training

Exercise training (ExT) improves skeletal muscle health via multiple adaptative pathways. Nrf2 is a principal antioxidant transcription factor responsible for maintaining intracellular redox homeostasis. In this study, we hypothesized that Nrf2 is essential for adaptative responses to ExT and thus b...

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Autores principales: Bhat, Anjali, Abu, Rafay, Jagadesan, Sankarasubramanian, Vellichirammal, Neetha Nanoth, Pendyala, Ved Vasishtha, Yu, Li, Rudebush, Tara L., Guda, Chittibabu, Zucker, Irving H., Kumar, Vikas, Gao, Lie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854705/
https://www.ncbi.nlm.nih.gov/pubmed/36671013
http://dx.doi.org/10.3390/antiox12010151
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author Bhat, Anjali
Abu, Rafay
Jagadesan, Sankarasubramanian
Vellichirammal, Neetha Nanoth
Pendyala, Ved Vasishtha
Yu, Li
Rudebush, Tara L.
Guda, Chittibabu
Zucker, Irving H.
Kumar, Vikas
Gao, Lie
author_facet Bhat, Anjali
Abu, Rafay
Jagadesan, Sankarasubramanian
Vellichirammal, Neetha Nanoth
Pendyala, Ved Vasishtha
Yu, Li
Rudebush, Tara L.
Guda, Chittibabu
Zucker, Irving H.
Kumar, Vikas
Gao, Lie
author_sort Bhat, Anjali
collection PubMed
description Exercise training (ExT) improves skeletal muscle health via multiple adaptative pathways. Nrf2 is a principal antioxidant transcription factor responsible for maintaining intracellular redox homeostasis. In this study, we hypothesized that Nrf2 is essential for adaptative responses to ExT and thus beneficial for muscle. Experiments were carried out on male wild type (WT) and iMS-Nrf2(flox/flox) inducible muscle-specific Nrf2 (KO) mice, which were randomly assigned to serve as sedentary controls (Sed) or underwent 3 weeks of treadmill ExT thus generating four groups: WT-Sed, WT-ExT, KO-Sed, and KO-ExT groups. Mice were examined for exercise performance and in situ tibialis anterior (TA) contractility, followed by mass spectrometry-based proteomics and bioinformatics to identify differentially expressed proteins and signaling pathways. We found that maximal running distance was significantly longer in the WT-ExT group compared to the WT-Sed group, whereas this capacity was impaired in KO-ExT mice. Force generation and fatigue tolerance of the TA were enhanced in WT-ExT, but reduced in KO-ExT, compared to Sed controls. Proteomic analysis further revealed that ExT upregulated 576 proteins in WT but downregulated 207 proteins in KO mice. These proteins represent pathways in redox homeostasis, mitochondrial respiration, and proteomic adaptation of muscle to ExT. In summary, our data suggest a critical role of Nrf2 in the beneficial effects of SkM and adaptation to ExT.
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spelling pubmed-98547052023-01-21 Quantitative Proteomics Identifies Novel Nrf2-Mediated Adaptative Signaling Pathways in Skeletal Muscle Following Exercise Training Bhat, Anjali Abu, Rafay Jagadesan, Sankarasubramanian Vellichirammal, Neetha Nanoth Pendyala, Ved Vasishtha Yu, Li Rudebush, Tara L. Guda, Chittibabu Zucker, Irving H. Kumar, Vikas Gao, Lie Antioxidants (Basel) Article Exercise training (ExT) improves skeletal muscle health via multiple adaptative pathways. Nrf2 is a principal antioxidant transcription factor responsible for maintaining intracellular redox homeostasis. In this study, we hypothesized that Nrf2 is essential for adaptative responses to ExT and thus beneficial for muscle. Experiments were carried out on male wild type (WT) and iMS-Nrf2(flox/flox) inducible muscle-specific Nrf2 (KO) mice, which were randomly assigned to serve as sedentary controls (Sed) or underwent 3 weeks of treadmill ExT thus generating four groups: WT-Sed, WT-ExT, KO-Sed, and KO-ExT groups. Mice were examined for exercise performance and in situ tibialis anterior (TA) contractility, followed by mass spectrometry-based proteomics and bioinformatics to identify differentially expressed proteins and signaling pathways. We found that maximal running distance was significantly longer in the WT-ExT group compared to the WT-Sed group, whereas this capacity was impaired in KO-ExT mice. Force generation and fatigue tolerance of the TA were enhanced in WT-ExT, but reduced in KO-ExT, compared to Sed controls. Proteomic analysis further revealed that ExT upregulated 576 proteins in WT but downregulated 207 proteins in KO mice. These proteins represent pathways in redox homeostasis, mitochondrial respiration, and proteomic adaptation of muscle to ExT. In summary, our data suggest a critical role of Nrf2 in the beneficial effects of SkM and adaptation to ExT. MDPI 2023-01-09 /pmc/articles/PMC9854705/ /pubmed/36671013 http://dx.doi.org/10.3390/antiox12010151 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bhat, Anjali
Abu, Rafay
Jagadesan, Sankarasubramanian
Vellichirammal, Neetha Nanoth
Pendyala, Ved Vasishtha
Yu, Li
Rudebush, Tara L.
Guda, Chittibabu
Zucker, Irving H.
Kumar, Vikas
Gao, Lie
Quantitative Proteomics Identifies Novel Nrf2-Mediated Adaptative Signaling Pathways in Skeletal Muscle Following Exercise Training
title Quantitative Proteomics Identifies Novel Nrf2-Mediated Adaptative Signaling Pathways in Skeletal Muscle Following Exercise Training
title_full Quantitative Proteomics Identifies Novel Nrf2-Mediated Adaptative Signaling Pathways in Skeletal Muscle Following Exercise Training
title_fullStr Quantitative Proteomics Identifies Novel Nrf2-Mediated Adaptative Signaling Pathways in Skeletal Muscle Following Exercise Training
title_full_unstemmed Quantitative Proteomics Identifies Novel Nrf2-Mediated Adaptative Signaling Pathways in Skeletal Muscle Following Exercise Training
title_short Quantitative Proteomics Identifies Novel Nrf2-Mediated Adaptative Signaling Pathways in Skeletal Muscle Following Exercise Training
title_sort quantitative proteomics identifies novel nrf2-mediated adaptative signaling pathways in skeletal muscle following exercise training
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854705/
https://www.ncbi.nlm.nih.gov/pubmed/36671013
http://dx.doi.org/10.3390/antiox12010151
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