Mechanical regulation of cardiac myocyte protein turnover and myofibrillar structure.
Mechanical forces play an essential role in regulating the synthesis and assembly of contractile proteins into the sarcomeres of cardiac myocytes. To examine if physical forces might also regulate the turnover of contractile proteins at a posttranslational site of control, beating and nonbeating neonatal cardiac myocytes (NCM) were subjected to a 5% static stretch. The L-type calcium channel blocker nifedipine (12 microM) was used to inhibit contraction. Pulse-chase biosynthetic labeling experiments demonstrated that contractile arrest accelerated the loss of isotopic tracer from the total myofibrillar protein fraction, myosin heavy chain (MHC), and actin, but not desmin. Myofibrillar abnormalities developed in parallel with these metabolic changes. A 5% static load appeared to partially stabilize myofibrillar structure in nonbeating NCM and suppressed the loss of isotopic tracer from the total myofibrillar protein fraction, MHC, and actin in beating and nonbeating NCM. Contractile activity and/or a static stretch promoted the accumulation of MHC, actin, and desmin. Applying a static load to myocytes that lacked preexisting myofibrils did not promote the assembly of sarcomeres or alter protein turnover. These data indicate that the turnover of MHC and actin is correlated with the organizational state of the myofibrillar apparatus.
Simpson
D G
DG
Department of Developmental Biology and Anatomy, University of South Carolina School of Medicine, Columbia 29208, USA.
Sharp
W W
WW
Borg
T K
TK
Price
R L
RL
Terracio
L
L
Samarel
A M
AM
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D009210:Myofibrils / Q000648:ultrastructure*; D010812:Physical Stimulation; D051381:Rats
D003285:Contractile Proteins