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.
Ku
Z
Z
Department of Physiology and Biophysics, University of Tennessee Health Science Center, Memphis 38163, USA.
Yang
J
J
Menon
V
V
Thomason
D B
DB
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006614:Hindlimb; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D010441:Peptide Chain Elongation, Translational; D010766:Phosphorylation; D010769:Phosphothreonine / Q000032:analysis; D011132:Polyribosomes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012044:Regression Analysis
D018840:HSP70 Heat-Shock Proteins; D009124:Muscle Proteins; D010769:Phosphothreonine; D000255:Adenosine Triphosphate; D007930:Leucine