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Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting
Skeletal muscle (SM) regeneration after injury is impaired by excessive inflammation. Particularly, the inflammatory cytokine tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent inducer of skeletal muscle wasting and fibrosis. In this study we investigated the role of Nrf...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887379/ https://www.ncbi.nlm.nih.gov/pubmed/24406502 http://dx.doi.org/10.1038/srep03625 |
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author | Al-Sawaf, Othman Fragoulis, Athanassios Rosen, Christian Kan, Yuet Wai Sönmez, Tolga Taha Pufe, Thomas Wruck, Christoph Jan |
author_facet | Al-Sawaf, Othman Fragoulis, Athanassios Rosen, Christian Kan, Yuet Wai Sönmez, Tolga Taha Pufe, Thomas Wruck, Christoph Jan |
author_sort | Al-Sawaf, Othman |
collection | PubMed |
description | Skeletal muscle (SM) regeneration after injury is impaired by excessive inflammation. Particularly, the inflammatory cytokine tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent inducer of skeletal muscle wasting and fibrosis. In this study we investigated the role of Nrf2, a major regulator of oxidative stress defence, in SM ischemia/reperfusion (I/R) injury and TWEAK induced atrophy. We explored the time-dependent expression of TWEAK after I/R in SM of Nrf2-wildtype (WT) and knockout (KO) mice. Nrf2-KO mice expressed significant higher levels of TWEAK as compared to WT mice. Consequently, Nrf2-KO mice present an insufficient regeneration as compared to Nrf2-WT mice. Moreover, TWEAK stimulation activates Nrf2 in the mouse myoblast cell line C2C12. This Nrf2 activation inhibits TWEAK induced atrophy in C2C12 differentiated myotubes. In summary, we show that Nrf2 protects SM from TWEAK-induced cell death in vitro and that Nrf2-deficient mice therefore have poorer muscle regeneration. |
format | Online Article Text |
id | pubmed-3887379 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-38873792014-01-10 Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting Al-Sawaf, Othman Fragoulis, Athanassios Rosen, Christian Kan, Yuet Wai Sönmez, Tolga Taha Pufe, Thomas Wruck, Christoph Jan Sci Rep Article Skeletal muscle (SM) regeneration after injury is impaired by excessive inflammation. Particularly, the inflammatory cytokine tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent inducer of skeletal muscle wasting and fibrosis. In this study we investigated the role of Nrf2, a major regulator of oxidative stress defence, in SM ischemia/reperfusion (I/R) injury and TWEAK induced atrophy. We explored the time-dependent expression of TWEAK after I/R in SM of Nrf2-wildtype (WT) and knockout (KO) mice. Nrf2-KO mice expressed significant higher levels of TWEAK as compared to WT mice. Consequently, Nrf2-KO mice present an insufficient regeneration as compared to Nrf2-WT mice. Moreover, TWEAK stimulation activates Nrf2 in the mouse myoblast cell line C2C12. This Nrf2 activation inhibits TWEAK induced atrophy in C2C12 differentiated myotubes. In summary, we show that Nrf2 protects SM from TWEAK-induced cell death in vitro and that Nrf2-deficient mice therefore have poorer muscle regeneration. Nature Publishing Group 2014-01-10 /pmc/articles/PMC3887379/ /pubmed/24406502 http://dx.doi.org/10.1038/srep03625 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Al-Sawaf, Othman Fragoulis, Athanassios Rosen, Christian Kan, Yuet Wai Sönmez, Tolga Taha Pufe, Thomas Wruck, Christoph Jan Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting |
title | Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting |
title_full | Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting |
title_fullStr | Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting |
title_full_unstemmed | Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting |
title_short | Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting |
title_sort | nrf2 protects against tweak-mediated skeletal muscle wasting |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887379/ https://www.ncbi.nlm.nih.gov/pubmed/24406502 http://dx.doi.org/10.1038/srep03625 |
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