PA700

                     

                                           Base Subunits

                                             Rpt2

                                                                                    Rpn10   Rpt4   

                                          Rpt1    Rpt5

PA700

 

EFEF

EF

 

 
                                          Rpt2    Rpt6                                                                                                                                                          

      

 

                                                                Rpn3     Rpn5

                                                                Rpn6      Rpn7

                                                                Rpn8      Rpn9

                                                                Rpn10    Rpn12

 

 

Myofibrillar protein degradation is mediated through the ubiquitin-proteasome pathway. To investigate if altered proteasome activity plays a role in age-related muscle atrophy, we examined muscle size and proteasome function in young and aged F344BN rats. Significant age-related muscle atrophy was confirmed by the 38% decrease in cross-sectional area of type 1 fibers in soleus muscle. Determination of proteasome function showed hydrolysis of fluorogenic peptides was equivalent between ages. However, when accounting for the 3-fold increase in content of the 20S catalytic core in aged muscle, the lower specific activity suggests a functional loss in individual proteins with aging. Comparing the composition of the catalytic beta-subunits showed an age-related 4-fold increase in the cytokine-inducible subunits, LMP2 and LMP7. Additionally, the content of the activating complexes, PA28 and PA700, relative to the 20S proteasome was reduced 50%. These results suggest significant alterations in the intrinsic activity, the percentage of immunoproteasome, and the regulation of the 20S proteasome by PA28 and PA700 in aged muscle.

PMID: 14678786 [PubMed - indexed for MEDLINE]