PMID- 21209383
OWN - NLM
STAT- MEDLINE
DCOM- 20110509
LR  - 20211020
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 300
IP  - 3
DP  - 2011 Mar
TI  - IkappaBalpha degradation is necessary for skeletal muscle atrophy associated with 
      contractile claudication.
PG  - R595-604
LID - 10.1152/ajpregu.00728.2010 [doi]
AB  - The arterial blockage in patients with peripheral arterial disease (PAD) 
      restricts oxygen delivery to skeletal muscles distal to the blockage. In 
      advanced-stage PAD patients, this creates a chronic ischemic condition in the 
      affected muscles. However, in the majority of PAD patients, the muscles distal to 
      the blockage only become ischemic during physical activity when the oxygen 
      demands of these muscles are increased. Therefore, the skeletal muscle of most 
      PAD patients undergoes repeated cycles of low-grade ischemia-reperfusion each 
      time the patient is active and then rests. This has been speculated to contribute 
      to the biochemical and morphological myopathies observed in PAD patients. The 
      current study aimed to determine, using a rodent model, whether repeated hind 
      limb muscle contractions during blood flow restriction to the hind limb muscles 
      increases NF-kappaB activity. We, subsequently, determined whether an increase in 
      NF-kappaB activity during this condition is required for the increased transcription 
      of specific atrophy-related genes and muscle fiber atrophy. We found that hind 
      limb muscle contractions during blood flow restriction to the limb increased 
      NF-kappaB activity, the transcription of specific atrophy-related genes, and caused a 
      35% decrease in muscle fiber cross-sectional area. We further found that 
      inhibition of NF-kappaB activity, via gene transfer of a dominant-negative inhibitor 
      of kappaBalpha (d.n. IkappaBalpha), prevented the increase in atrophy gene expression and muscle 
      fiber atrophy. These findings demonstrate that when blood flow to skeletal muscle 
      is restricted, repeated cycles of muscle contraction can cause muscle fiber 
      atrophy that requires NF-kappaB-IkappaBalpha signaling.
FAU - Hain, Brian A
AU  - Hain BA
AD  - Department of Applied Physiology, Univ. of Florida, Gainesville, 32611, USA.
FAU - Dodd, Stephen L
AU  - Dodd SL
FAU - Judge, Andrew R
AU  - Judge AR
LA  - eng
GR  - P30 AG028740/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110105
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, rat)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Electric Stimulation
MH  - Electroporation
MH  - Gene Expression Regulation
MH  - Gene Transfer Techniques
MH  - Hindlimb
MH  - I-kappa B Proteins/genetics/*metabolism
MH  - Intermittent Claudication/genetics/*metabolism/pathology/physiopathology
MH  - Ischemia/genetics/*metabolism/pathology/physiopathology
MH  - Ligation
MH  - Male
MH  - *Muscle Contraction
MH  - Muscle, Skeletal/blood supply/*metabolism/pathology/physiopathology
MH  - Muscular Atrophy/genetics/*metabolism/pathology/physiopathology
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Fusion Proteins/metabolism
MH  - Regional Blood Flow
MH  - Time Factors
MH  - Transcription, Genetic
PMC - PMC6195647
EDAT- 2011/01/07 06:00
MHDA- 2011/05/10 06:00
PMCR- 2012/03/01
CRDT- 2011/01/07 06:00
PHST- 2011/01/07 06:00 [entrez]
PHST- 2011/01/07 06:00 [pubmed]
PHST- 2011/05/10 06:00 [medline]
PHST- 2012/03/01 00:00 [pmc-release]
AID - ajpregu.00728.2010 [pii]
AID - R-00728-2010 [pii]
AID - 10.1152/ajpregu.00728.2010 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2011 Mar;300(3):R595-604. doi: 
      10.1152/ajpregu.00728.2010. Epub 2011 Jan 5.