title: Proteasome production in human muscle during nutritional inhibition of myofibrillar protein degradation.
abstract: Protein undernutrition inhibits adenosine triphosphate (ATP)-dependent muscle protein degradation-a hallmark of the proteasome system. Here we report decreased myofibrillar protein degradation during dietary protein restriction without a concomitant decrease in proteasome gene expression, proteasome protein abundance, or proteasome in vivo fractional synthesis rate. Healthy human subjects consuming the average minimum adult protein requirement (0.71 g x kg(-1) fat-free mass x d(-1)) exhibited substantially lower (68%) excretion of 3-methylhistidine, an indicator of myofibrillar protein breakdown, when compared with subjects consuming an ample, American-style protein intake (1.67 g x kg(-1) fat-free mass x d(-1)). However, they displayed no difference in the expression of mRNA for proteasome subunits C2 or C3, in the content of C2 protein, or in the rate of incorporation of stable isotopically labeled l-[1-(13)C]-leucine into proteasome proteins. The results demonstrate that nutritional inhibition of myofibrillar protein degradation does not involve suppression in vivo of proteasome production in man. This suggests that other elements of the ubiquitin-proteasome system, such as ubiquitination pathways, are more important than proteasome abundance in the nutritional regulation of skeletal muscle mass.
authors.affiliation: Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Irwin G
authors.initials: IG
authors.lastname: Brodsky
authors.forename: Dennis
authors.initials: D
authors.lastname: Suzara
authors.forename: Mikhail
authors.initials: M
authors.lastname: Furman
authors.forename: Paul
authors.initials: P
authors.lastname: Goldspink
authors.forename: G Charles
authors.initials: GC
authors.lastname: Ford
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
authors.forename: Jayme
authors.initials: J
authors.lastname: Kukowski
authors.forename: Sheryl
authors.initials: S
authors.lastname: Bedno
mesh_terms: D000293:Adolescent; D000328:Adult; D001806:Blood Urea Nitrogen; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D004032:Diet; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008297:Male; D008762:Methylhistidines / Q000652:urine; D009097:Multienzyme Complexes / Q000096:biosynthesis*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008762:Methylhistidines; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D012333:RNA, Messenger; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D007930:Leucine; C028118:3-methylhistidine