The IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy.

Authors: Van Gammeren, D  Damrauer, JS  Jackman, RW  Kandarian, SC 
Citation: Van Gammeren D, etal., FASEB J. 2009 Feb;23(2):362-70. doi: 10.1096/fj.08-114249. Epub 2008 Sep 30.
Pubmed: (View Article at PubMed) PMID:18827022
DOI: Full-text: DOI:10.1096/fj.08-114249

Nuclear factor-kappaB (NF-kappaB) signaling is necessary for many types of muscle atrophy, yet only some of the required components have been identified. Gene transfer of a dominant negative (d.n.) IKKbeta into rat soleus muscles showed complete inhibition of 7-day disuse-induced activation of a kappaB reporter gene, while overexpression of wild-type (w.t.) IKKbeta did not. Overexpression of a d.n. IKKbeta-EGFP fusion protein showed that atrophy was inhibited by 50%, indicating that IKKbeta is required for the atrophy process. Overexpression of constitutively active (c.a.) IKKbeta-EGFP showed a marked increase in NF-kappaB activity and a decrease in fiber size of weight-bearing soleus muscles, while muscles overexpressing w.t. IKKbeta-HA had no effect. The same results were found for IKKalpha; overexpression of a d.n. form of the protein decreased unloading-induced NF-kappaB activation and inhibited atrophy by 50%, while overexpression of the w.t. protein had no effect. Overexpression of a c.a. IKKalpha-EGFP fusion protein showed that IKKalpha was sufficient to activate NF-kappaB activity and induce fiber atrophy in muscle. Overexpression of d.n. IKKbeta plus d.n. IKKalpha showed an additive effect on the inhibition of disuse atrophy (70%), suggesting that both kinases of the IKK complex are required for muscle atrophy. These data show that both IKKalpha and IKKbeta are necessary and sufficient for physiological muscle atrophy.

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CRRD Object Information
CRRD ID: 7495773
Created: 2013-12-12
Species: All species
Last Modified: 2013-12-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.