Control of protein balance in hypertrophied cardiac muscle
The levels of intracellular proteins are determined by a balance between their rates of synthesis and degradation. During the development of regression of cardiac hypertrophy, both of these rates can be expected to change. Possible control sites of synthetic and degradation processes are discussed in this article. The following experimental results are presented: (1) Cardiac mitochondrial cytochromes accumulate early after imposition of pressure overload, as a result of an increased rate of synthesis and decreased rate of degradation. (2) The half-life of myosin heavy chains (HC) in the steady state was determined from incorporation kinetics, using leucyl-tRNA as precursor, to be 5 to 6 days. (3) The existence of a pool of newly synthesized myofilaments which are not fully incorporated into the core of myofibrils is indicated by the incorporation data. Loosely bound myofilaments are labeled more extensively than the core myofibrils. Rapid mixing of this pool with the rest of the myofibrils is indicated by equalization of radioactivities at later time intervals. A precursor pool of light chains (LC) is also suggested by the time course of leucine incorporation. As a result of differences in the macromolecular precursor pool and in the rates of synthesis, the labeling of myofibrillar proteins varies in the following order: HC approximately equal to ..cap alpha..-actinin approximately equal to tropomyosin > actin > LC/sub 1/ approximately equal to LC/sub 2/. (4) The postmitochondrial supernatant fraction of muscle homogenate contains a calcium-activated neutral protease which specifically removes Z lines and ..cap alpha..-actinin from isolated myofibrils. Some of the properties of the enzyme, which was purified more than 200-fold, are described.
- Research Organization:
- Univ. of Chicago
- OSTI ID:
- 7124639
- Journal Information:
- Circ. Res.; (United States), Journal Name: Circ. Res.; (United States) Vol. 38:5; ISSN CIRUA
- Country of Publication:
- United States
- Language:
- English
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