Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF-κB
- PMID: 21771249
- PMCID: PMC5028794
- DOI: 10.1111/j.1474-9726.2011.00734.x
Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF-κB
Erratum in
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Erratum.Aging Cell. 2016 Oct;15(5):981-2. doi: 10.1111/acel.12457. Aging Cell. 2016. PMID: 27599757 Free PMC article. No abstract available.
Abstract
Abnormal levels of reactive oxygen species (ROS) and inflammatory cytokines have been observed in the skeletal muscle during muscle wasting including sarcopenia. However, the mechanisms that signal ROS production and prolonged maintenance of ROS levels during muscle wasting are not fully understood. Here, we show that myostatin (Mstn) is a pro-oxidant and signals the generation of ROS in muscle cells. Myostatin, a transforming growth factor-β (TGF-β) family member, has been shown to play an important role in skeletal muscle wasting by increasing protein degradation. Our results here show that Mstn induces oxidative stress by producing ROS in skeletal muscle cells through tumor necrosis factor-α (TNF-α) signaling via NF-κB and NADPH oxidase. Aged Mstn null (Mstn(-/-) ) muscles, which display reduced sarcopenia, also show an increased basal antioxidant enzyme (AOE) levels and lower NF-κB levels indicating efficient scavenging of excess ROS. Additionally, our results indicate that both TNF-α and hydrogen peroxide (H(2) O(2) ) are potent inducers of Mstn and require NF-κB signaling for Mstn induction. These results demonstrate that Mstn and TNF-α are components of a feed forward loop in which Mstn triggers the generation of second messenger ROS, mediated by TNF-α and NADPH oxidase, and the elevated TNF-α in turn stimulates Mstn expression. Higher levels of Mstn in turn induce muscle wasting by activating proteasomal-mediated catabolism of intracellular proteins. Thus, we propose that inhibition of ROS induced by Mstn could lead to reduced muscle wasting during sarcopenia.
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
Figures
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References
-
- Aiken J, Bua E, Cao Z, Lopez M, Wanagat JON, McKenzie D, McKiernan S (2002) Mitochondrial DNA deletion mutations and sarcopenia. Ann. N Y Acad. Sci. 959, 412–423. - PubMed
-
- Baumann AP, Ibebunjo C, Grasser WA, Paralkar VM (2003) Myostatin expression in age and denervation‐induced skeletal muscle atrophy. J. Musculoskelet. Neuronal Interact. 3, 8–16. - PubMed
-
- Beers RF, Sizer IW (1952) A Spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J. Biol. Chem. 195, 133–140. - PubMed
-
- Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein‐dye binding. Anal. Biochem. 72, 248–254. - PubMed
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