The temporal responses of protein synthesis, gene expression and cell signalling in human quadriceps muscle and patellar tendon to disuse.
We hypothesized that rates of myofibrillar and patellar tendon collagen synthesis would fall over time during disuse, the changes being accompanied in muscle by decreases in focal adhesion kinase (FAK) phosphorylation and in gene expression for proteolytic enzymes. We studied nine men (22 +/- 4 years, BMI 24 +/- 3 kg m(-2) (means +/- s.d.) who underwent unilateral lower leg suspension for 23 days; five were studied between 0 and 10 days and four between 10 and 21 days. Muscle and tendon biopsies were taken in the postabsorptive state at days 0, 10 and 21 for measurement of protein synthesis, gene expression and protein phosphorylation. Muscle cross-sectional area decreased by 5.2% at 14 days and 10.0% (both P < 0.001), at 23 days, i.e. 0.5% day(-1), whereas tendon dimensions were constant. Rates of myofibrillar protein synthesis fell (P < 0.01) from 0.047% h(-1) at day 0 to 0.022% h(-1) at 10 days without further changes. Tendon collagen synthetic rates also fell (P < 0.01), from 0.052 to 0.023% h(-1) at 10 days and then to 0.010% h(-1) at 21 days. FAK phosphorylation decreased 30% (P < 0.01) at 10 days. No changes occurred in the amounts/phosphorylation of PKB-P70s6k-mTOR pathway components. Expression of mRNA for MuRF-1 increased approximately 3-fold at 10 days without changes in MAFbx or tripeptidyl peptidase II mRNA, but all decreased between 10 and 21 days. Thus, both myofibrillar and tendon protein synthetic rates show progressive decreases during 21 days of disuse; in muscle, this is accompanied by decreased phosphorylation of FAK, with no marked increases in genes for proteolytic enzymes.
de Boer
Maarten D
MD
Instititute for Biophysical and Clinical Research into Human Movement, Manchester Metropolitan University, Alsager ST7 2HL, UK.
Selby
Anna
A
Atherton
Philip
P
Smith
Ken
K
Seynnes
Olivier R
OR
Maganaris
Constantinos N
CN
Maffulli
Nicola
N
Movin
Tomas
T
Narici
Marco V
MV
Rennie
Michael J
MJ
D000328:Adult; D000626:Aminopeptidases; D001706:Biopsy; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D020966:Muscular Disorders, Atrophic / Q000378:metabolism* / Q000473:pathology; D055435:Myostatin; D017847:Patellar Ligament / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D052097:Quadriceps Muscle / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
D024042:Collagen Type I; C525911:MSTN protein, human; D009124:Muscle Proteins; D055435:Myostatin; D016212:Transforming Growth Factor beta; D000070584:Tripartite Motif Proteins; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases