HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/C372    most recent 00293.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Judge, A. R. Articles by Kandarian, S. C. Search for Related Content PubMed PubMed Citation Articles by Judge, A. R. Articles by Kandarian, S. C.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Role for IB, but not c-Rel, in skeletal muscle atrophy

¹Department of Health Sciences, Boston University, Boston; ²Genzyme, Waltham, Massachusetts; and ³Division of Immunology, Department of Medicine, Weill School of Medicine, Cornell University, New York, New York

Submitted 26 May 2006 ; accepted in final form 11 August 2006

Skeletal muscle atrophy is associated with a marked and sustained activation of nuclear factor-B (NF-B) activity. Previous work showed that p50 is one of the NF-B family members 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. Because endogenous inhibitory factor B (IB) was activated (i.e., decreased) at 3 and 7 days of muscle disuse (i.e., hindlimb unloading), we also tested if IB, which binds and retains Rel proteins in the cytosol, is required for atrophy and intermediates of the atrophy process. To do this, we electrotransferred a dominant negative IB (IBN) in soleus muscles, which were either unloaded or weight bearing. 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 certain genes known to be upregulated with atrophy were significantly inhibited by IBN expression 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 for atrophy 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 the role of NF-B/IB family members in skeletal muscle atrophy, and they provide new candidate NF-B target genes for further study.

disuse; nuclear factor-B signaling; unloading; muscle wasting; ubiquitination; atrophy genes; inhibitory factor B

This article has been cited by other articles:

				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]