Protein metabolism and beta-myosin heavy-chain mRNA in unweighted soleus muscle.
To investigate the relative influence of protein synthetic and degradative control mechanisms in vivo during skeletal muscle atrophy, we measured myofibril and total mixed protein synthesis rates in muscles of rats prevented from hindlimb weight-bearing for 5 h and 7 days. Protein synthesis rates were determined by infusing the animals with [3H]Leu for 5 h and measuring the specific activity of [3H]Leu in the aminoacyl-tRNA precursor and protein product fractions of the muscles. In the soleus muscle, myofibril protein synthesis rates decreased from a control value of 5.9 to 4.6%/day during 5 h of hindlimb unweighting and to 2.4%/day after 7 days of hindlimb unweighting. The relatively more phasic muscles (plantaris, medial gastrocnemius, quadriceps) showed a tendency for increased myofibril protein synthesis rates (117-127% of control) during the first 5 h followed by a decrease (46-62% of control) at 7 days of hindlimb unweighting. A predicted time course of soleus muscle myofibril protein degradation rate was obtained from a numerical model of the decrease in soleus myofibril protein synthesis rate as a first-order process [half-time (t1/2) = 0.3 day by least-squares fit] and the time course of soleus muscle myofibril protein previously observed with hindlimb unweighting (Thomason et al., J. Appl. Physiol. 63: 130-137, 1987). The degradation rate model makes specific, testable predictions for the mechanism of myofibril protein degradation during soleus muscle atrophy: 1) the first-order degradation rate constant does not obtain a fixed value over a 24-day period but is continuously changing throughout atrophy, and 2) the first-order degradation rate constant changes on a time scale slower than protein synthesis rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Thomason
D B
DB
Department of Physiology and Cell Biology, University of Texas Medical School, Houston 77225.
Biggs
R B
RB
Booth
F W
FW
D000818:Animals; D001284:Atrophy; D005260:Female; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D009132:Muscles / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D015879:Myosin Subfragments; D009218:Myosins / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics*; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D015879:Myosin Subfragments; D010446:Peptide Fragments; D011506:Proteins; D012333:RNA, Messenger; D012346:RNA, Transfer, Amino Acyl; D009218:Myosins; D007930:Leucine