Decreased polysomal HSP-70 may slow polypeptide elongation during skeletal muscle atrophy.

Slowed elongation rate is the apparent cause of the rapid decrease in rat soleus muscle protein synthesis rate during non-weight bearing. We found that elongation factor 2 was not phosphorylated and thus could not explain the slowed elongation rate. However, we observed a 44 +/- 19 and 28 +/- 14% decrease in the chaperone protein 70-kDa heat-shock cognate/heat shock protein (HSC/HSP-70) associated with the polysomes after 12 and 18 h of non-weight bearing, respectively. Size-fractionated polysomes had less HSC/HSP-70 associated with the larger polysomes in 18-h non-weight-bearing soleus muscle. ATP concentration increased in the non-weight-bearing muscle, so, because ATP enhances HSC/HSP-70 dissociation, we tested the potential role of ATP. Digitonin-permeabilized myoblasts treated with increasing concentrations of ATP showed both a decreased association of HSC/HSP-70 with the polysomes and a shift toward heavier polysomes; these responses were blocked by adenosine 5'-O-(3-thiotriphosphate). These data are consistent with the role of HSC/HSP-70 as a chaperone of nascent protein. The absence of HSC/HSP-70 may slow ribosome translocation, thus slowing elongation rate.