Attenuation of @entity2057 in a @entity19 model of XXXX by inhibition of the dsRNA-dependent protein kinase.

@entity308 @entity52768 @entity5 @entity19 @entity3085 @entity2057
Atrophy of skeletal muscle is due to a @entity308 in protein synthesis and an increase in degradation. Studies in vitro have suggested that activation of the dsRNA-dependent protein kinase ( @entity52768 ) may be responsible for these changes in protein synthesis and degradation. In order to evaluate whether this is also applicable to @entity5 the action of a @entity52768 inhibitor on the development of @entity3085 has been studied in @entity19 bearing the MAC16 @entity5 . Treatment of animals with the @entity52768 inhibitor (5 mg kg(-1)) significantly reduced levels of phospho- @entity52768 in muscle down to that found in non- @entity5 -bearing @entity19 , and effectively attenuated the @entity308 of body weight, with increased muscle mass, and also inhibited @entity5 growth. There was an increase in protein synthesis in skeletal muscle, which paralleled a decrease in eukaryotic initiation factor 2alpha phosphorylation. Protein degradation rates in skeletal muscle were also significantly decreased, as was proteasome activity levels and expression. Myosin levels were increased up to values found in non- @entity5 -bearing animals. Proteasome expression correlated with a decreased nuclear accumulation of nuclear factor-kappaB (NF-kappaB). The @entity52768 inhibitor also significantly inhibited @entity5 growth, although this appeared to be a separate event from the effect on @entity2057 . These results suggest that inhibition of the autophosphorylation of @entity52768 may represent an appropriate target for the attenuation of @entity2057 in @entity5 .
