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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-9854705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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