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Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise

Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers, mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo, but...

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Autores principales: Henríquez-Olguin, Carlos, Knudsen, Jonas R., Raun, Steffen H., Li, Zhencheng, Dalbram, Emilie, Treebak, Jonas T., Sylow, Lykke, Holmdahl, Rikard, Richter, Erik A., Jaimovich, Enrique, Jensen, Thomas E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789013/
https://www.ncbi.nlm.nih.gov/pubmed/31604916
http://dx.doi.org/10.1038/s41467-019-12523-9
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author Henríquez-Olguin, Carlos
Knudsen, Jonas R.
Raun, Steffen H.
Li, Zhencheng
Dalbram, Emilie
Treebak, Jonas T.
Sylow, Lykke
Holmdahl, Rikard
Richter, Erik A.
Jaimovich, Enrique
Jensen, Thomas E.
author_facet Henríquez-Olguin, Carlos
Knudsen, Jonas R.
Raun, Steffen H.
Li, Zhencheng
Dalbram, Emilie
Treebak, Jonas T.
Sylow, Lykke
Holmdahl, Rikard
Richter, Erik A.
Jaimovich, Enrique
Jensen, Thomas E.
author_sort Henríquez-Olguin, Carlos
collection PubMed
description Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers, mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo, but whether myocellular ROS production is stimulated by in vivo exercise to control metabolism is unclear. Here, we combined exercise in humans and mice with fluorescent dyes, genetically-encoded biosensors, and NADPH oxidase 2 (NOX2) loss-of-function models to demonstrate that NOX2 is the main source of cytosolic ROS during moderate-intensity exercise in skeletal muscle. Furthermore, two NOX2 loss-of-function mouse models lacking either p47phox or Rac1 presented striking phenotypic similarities, including greatly reduced exercise-stimulated glucose uptake and GLUT4 translocation. These findings indicate that NOX2 is a major myocellular ROS source, regulating glucose transport capacity during moderate-intensity exercise.
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spelling pubmed-67890132019-10-15 Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise Henríquez-Olguin, Carlos Knudsen, Jonas R. Raun, Steffen H. Li, Zhencheng Dalbram, Emilie Treebak, Jonas T. Sylow, Lykke Holmdahl, Rikard Richter, Erik A. Jaimovich, Enrique Jensen, Thomas E. Nat Commun Article Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers, mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo, but whether myocellular ROS production is stimulated by in vivo exercise to control metabolism is unclear. Here, we combined exercise in humans and mice with fluorescent dyes, genetically-encoded biosensors, and NADPH oxidase 2 (NOX2) loss-of-function models to demonstrate that NOX2 is the main source of cytosolic ROS during moderate-intensity exercise in skeletal muscle. Furthermore, two NOX2 loss-of-function mouse models lacking either p47phox or Rac1 presented striking phenotypic similarities, including greatly reduced exercise-stimulated glucose uptake and GLUT4 translocation. These findings indicate that NOX2 is a major myocellular ROS source, regulating glucose transport capacity during moderate-intensity exercise. Nature Publishing Group UK 2019-10-11 /pmc/articles/PMC6789013/ /pubmed/31604916 http://dx.doi.org/10.1038/s41467-019-12523-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Henríquez-Olguin, Carlos
Knudsen, Jonas R.
Raun, Steffen H.
Li, Zhencheng
Dalbram, Emilie
Treebak, Jonas T.
Sylow, Lykke
Holmdahl, Rikard
Richter, Erik A.
Jaimovich, Enrique
Jensen, Thomas E.
Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
title Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
title_full Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
title_fullStr Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
title_full_unstemmed Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
title_short Cytosolic ROS production by NADPH oxidase 2 regulates muscle glucose uptake during exercise
title_sort cytosolic ros production by nadph oxidase 2 regulates muscle glucose uptake during exercise
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789013/
https://www.ncbi.nlm.nih.gov/pubmed/31604916
http://dx.doi.org/10.1038/s41467-019-12523-9
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