PMID- 18827022
OWN - NLM
STAT- MEDLINE
DCOM- 20090216
LR  - 20181113
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 23
IP  - 2
DP  - 2009 Feb
TI  - The IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for 
      skeletal muscle atrophy.
PG  - 362-70
LID - 10.1096/fj.08-114249 [doi]
AB  - 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.
FAU - Van Gammeren, Darin
AU  - Van Gammeren D
AD  - Boston University, Boston, MA 02215, USA.
FAU - Damrauer, Jeffrey S
AU  - Damrauer JS
FAU - Jackman, Robert W
AU  - Jackman RW
FAU - Kandarian, Susan C
AU  - Kandarian SC
LA  - eng
GR  - F32 AR054265/AR/NIAMS NIH HHS/United States
GR  - R01 AR041705/AR/NIAMS NIH HHS/United States
GR  - R01 AR41705/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080930
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Animals
MH  - Female
MH  - Genes, Reporter/genetics
MH  - I-kappa B Kinase/genetics/*metabolism
MH  - Muscular Atrophy/*enzymology/genetics/pathology
MH  - NF-kappa B/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
PMC - PMC2630783
EDAT- 2008/10/02 09:00
MHDA- 2009/02/17 09:00
PMCR- 2010/02/01
CRDT- 2008/10/02 09:00
PHST- 2008/10/02 09:00 [pubmed]
PHST- 2009/02/17 09:00 [medline]
PHST- 2008/10/02 09:00 [entrez]
PHST- 2010/02/01 00:00 [pmc-release]
AID - fj.08-114249 [pii]
AID - 08-114249 [pii]
AID - 10.1096/fj.08-114249 [doi]
PST - ppublish
SO  - FASEB J. 2009 Feb;23(2):362-70. doi: 10.1096/fj.08-114249. Epub 2008 Sep 30.