Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / metabolism*
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Animals
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Atrophy / metabolism
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Binding Sites
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Cell Cycle Proteins
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Cysteine Endopeptidases / chemistry*
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Cysteine Endopeptidases / metabolism*
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Cysteine Proteinase Inhibitors / pharmacology
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Cytokines / metabolism
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Hydrolysis
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In Vitro Techniques
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Kinetics
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Leupeptins / pharmacology
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Male
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Multienzyme Complexes / chemistry*
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Multienzyme Complexes / metabolism*
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Muscle Proteins / analysis
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Muscle Proteins / biosynthesis
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Muscle Proteins / metabolism*
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Muscle, Skeletal / enzymology
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Muscle, Skeletal / metabolism*
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Muscle, Skeletal / pathology
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Oligopeptides / chemistry
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Oligopeptides / metabolism
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Proteasome Endopeptidase Complex
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Protein Biosynthesis
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Protein Subunits
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Proteins / analysis
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Rats
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Rats, Inbred F344
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Up-Regulation
Substances
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Cell Cycle Proteins
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Cysteine Proteinase Inhibitors
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Cytokines
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Leupeptins
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Multienzyme Complexes
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Muscle Proteins
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Oligopeptides
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PA700 proteasome activator
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Protein Subunits
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Proteins
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Psme1 protein, rat
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Psme2 protein, rat
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde