| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
B
, but not c-Rel, in skeletal muscle atrophy
1 Health Sciences, Boston University, Boston, Massachusetts, United States
2 Genzyme, Waltham, Massachusetts, United States
3 Medicine, Cornell University, New York, New York, United States
* To whom correspondence should be addressed. E-mail: skandar{at}bu.edu.
Skeletal muscle atrophy is associated with a marked and sustained activation of NF-
B activity. Previous work showed that p50 is one NF-B family member required for this activation and for muscle atrophy. In this work we tested whether another NF-B family member, c-Rel, is required for atrophy. Since endogenous IB
was activated at 3 and 7 days of muscle disuse (unloading) we also tested if the inhibitor of B (IB), which binds and retains Rel proteins in the cytosol, is required for atrophy and intermediates of the atrophy process. To do this we electrotransfered a dominant negative IB (IB
N) into soleus muscles, which were either unloaded or weightbearing. IBN expression abolished the unloading induced increase in both NF-B activation and total ubiquitinated protein. IBN inhibited unloading-induced fiber atrophy by 40%. The expression of genes known to be upregulated with atrophy were significantly inhibited by IBN during unloading, including MAFbx/atrogin-1, Nedd4, IEX, 4E-BP1, FOXO3a, and cathepsin L, suggesting these genes may be targets of NF-B transcription factors. In contrast, c-Rel was not required because the unloading-induced markers of atrophy were the same in c-Rel-/- and wild type mice. Thus, IB degradation is required for the unloading-induced decrease in fiber size, the increase in protein ubiquitination, activation of NF-B signaling, and the expression of specific atrophy genes, but c-Rel is not. These data represent a significant advance in our understanding of NF-B/IB family members in muscle atrophy and they provide new candidate NF-B target genes for further study.
This article has been cited by other articles:
|
|
 |
|
  S. L. Dodd, B. Hain, S. M. Senf, and A. R. Judge Hsp27 inhibits IKK{beta}-induced NF-{kappa}B activity and skeletal muscle atrophy FASEB J, October 1, 2009; 23(10): 3415 - 3423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Van Gammeren, J. S. Damrauer, R. W. Jackman, and S. C. Kandarian The I{kappa}B kinases IKK{alpha} and IKK{beta} are necessary and sufficient for skeletal muscle atrophy FASEB J, February 1, 2009; 23(2): 362 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Li, J. S. Moylan, M. A. Chambers, J. Smith, and M. B. Reid Interleukin-1 stimulates catabolism in C2C12 myotubes Am J Physiol Cell Physiol, January 1, 2009; 297(3): C706 - C714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Senf, S. L. Dodd, J. M. McClung, and A. R. Judge Hsp70 overexpression inhibits NF-{kappa}B and Foxo3a transcriptional activities and prevents skeletal muscle atrophy FASEB J, November 1, 2008; 22(11): 3836 - 3845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sandri Signaling in Muscle Atrophy and Hypertrophy Physiology, June 1, 2008; 23(3): 160 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Frost and C. H. Lang Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass J Appl Physiol, July 1, 2007; 103(1): 378 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Acharyya and D. C. Guttridge Cancer Cachexia Signaling Pathways Continue to Emerge Yet Much Still Points to the Proteasome Clin. Cancer Res., March 1, 2007; 13(5): 1356 - 1361. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
