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Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubesTumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.
Document ID
20040112544
Document Type
Reprint (Version printed in journal)
Authors
Li, Y. P.
(Baylor College of Medicine Houston, Texas 77030, United States)
Atkins, C. M.
Sweatt, J. D.
Reid, M. B.
Hamilton, S. L.
Date Acquired
August 21, 2013
Publication Date
March 1, 1999
Publication Information
Publication: Antioxidants & redox signalling
Volume: 1
Issue: 1
ISSN: 1523-0864
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL59878
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Musculoskeletal

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