Altered proteasome function and subunit composition in aged muscle.
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.
Husom
Aimee D
AD
Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, MN 55455, USA.
Peters
Elizabeth A
EA
Kolling
Erin A
EA
Fugere
Nicole A
NA
Thompson
LaDora V
LV
Ferrington
Deborah A
DA
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001284:Atrophy / Q000378:metabolism; D001665:Binding Sites; D018797:Cell Cycle Proteins; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D009124:Muscle Proteins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D021122:Protein Subunits; D011506:Proteins / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D015853:Cysteine Proteinase Inhibitors; D016207:Cytokines; D007976:Leupeptins; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D009842:Oligopeptides; C085834:PA700 proteasome activator; D021122:Protein Subunits; D011506:Proteins; C490050:Psme1 protein, rat; C490052:Psme2 protein, rat; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde