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Paraplegia in Rats is Associated with an Inhibition of p70S6 Kinase Activity
Author(s) -
Dreyer Hans C.,
DiCarlo Stephen E.,
Lujan Heidi L.,
Rasmussen Blake B.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1469-b
Subject(s) - ampk , skeletal muscle , medicine , endocrinology , pi3k/akt/mtor pathway , soleus muscle , protein kinase a , amp activated protein kinase , wasting , kinase , muscle atrophy , spinal cord , chemistry , biology , signal transduction , microbiology and biotechnology , neuroscience
Skeletal muscle p70S6 kinase is a downstream component of the mammalian target of rapamycin (mTOR) signaling pathway and a primary regulator of translation initiation and protein synthesis. Skeletal muscle AMP‐activated protein kinase (AMPKα 2) is a metabolic sensor of cellular energy status, an upstream regulator of mTOR, and has been recently identified as an inhibitor of muscle protein synthesis. The purpose of this study was to determine if p70S6K and AMPKα 2 activity are diminished in conditions associated with muscle wasting (i.e., spinal cord injury). Soleus muscle was collected from male Wistar rats 10 weeks following complete T 4‐5 spinal cord transection and in control sham operated rats. We utilized immunoprecipitation methods to measure p70S6 kinase and AMPKα 2 activity. Paraplegia was associated with a significant soleus muscle atrophy (33%, P < 0.05). p70S6K activity was significantly reduced following 10 weeks of spinal cord transection (50%, P < 0.05). Whereas, we found that basal AMPKα 2 activity was not altered (415 ± 55 vs. 452 ± 67 pmol·g −1 ·min −1 , P = 0.67, intact and spinal transected, respectively). We conclude that translation initiation in skeletal muscle is inhibited in a rat model of paraplegia since p70S6K activity was significantly reduced. Further analysis is necessary to determine if AMPK activity plays a role in muscle wasting, possibly affecting the protein synthesis rates and muscle cell size during the acute phase of spinal transection.