Regulatory Aspects of Protein Synthesis in Skeletal and Cardiac Muscle.

Mammalian cardiac and skeletal muscle in the adult animal demostrate a capacity to specifically adapt to increases in functional dem and and , in the case of skeletal muscle, to in toto transplantation. It is clear that qualitative and quantitative changes in the synthesis of muscle protein occur during the adaptive process. Which molecular parameters regulate the extent and nature of the adaptive process is unknown. Selected aspects of the protein synthetic system of cardiac and skeletal muscle were analyzed following treatment with Marcaine, a myotoxic drug, and Isoproterenol, a (beta)-adrenergic stimulator transplantation and exhaustive exercise. Whole tissue explant cultures of the gastrocnemius muscle of guinea pigs forced to run to exhaustion on a motor-driven treadmill incorporated significantly more amino acid into protein than did control cultures. An in vitro protein synthesizing system containing polyribosomes isolated from the lower rear leg of exhausted animals were able to direct the synthesis of 50% more polypeptide than control polyribosomes. Polyadenylated messenger RNA that coded for proteins of molecular weight 230,000 - 17,000 daltons was isolated from rat cardiac and skeletal muscle and translated in vitro with high efficiency in a translation system derived from wheat germ. This procedure was used to assess the effect of Marcaine, a myotoxic drug, on the rat tibialis anterior muscle. The relative proportion of myosin heavy chain and actin synthesized decreased by 5.1% and increased 3.4% one and 10 days after a single injection of Marcaine, corresponding to a degenerative and regenerative process in the muscle. These same procedures were utilized to examine the effects of Isoproterenol, a (beta)-adrenergic stimulator, on rat cardiac muscle. Twenty hours following three injections of the drug (5 mg/kg) the relative proportion of myofibrillar protein (synthesized in a cell-free system increased by 8%. These effects were dependent on both time and dose regime. Rat extensor digitorum longus muscle undergoes a rapid degeneration and regeneration following in toto transplantation with neural supply left intact. The low molecular weight subunits of myosin (LC(,1-3)) were qualitatively and quantitatively analyzed using polyacrylamide gel electrophoresis 10, 20 and 140 days following nerve-intact transplantation. The relative mass of the LC's increased during this period and showed a correlation to the specific activity of the myosin adenosine triphosphatase. LC(,3) was not present at 10 days following transplantation. At 140 days the structure and enzyme activity of myosin isolated from transplanted muscle was identical to control muscle. The results of these experiments when analyzed in view of other reports suggest that specific qualitative and quantitative changes in the synthesis of myfibrillar proteins occurs during adaptation of skeletal and cardiac muscle following certain experimental treatment.PhDBiologyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/157818/1/8017351.pd