Studies of a factor from dystrophic mouse muscle inhibitory towards protein synthesis

Abstract

A substance inhibitory to protein synthesis was purified from mouse skeletal muscle by gel filtration and ion-exchange chromatography, as well as by centrifugation on sucrose gradients. The molecular weight of the inhibitor, determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, was 71000. The inhibitory activity was insensitive to ribonuclease A, deoxyribonuclease I and phospholipase C. It was sensitive to Pronase treatment but insensitive to heat-treatment and trypsin degradation. The present results, taken together with previous studies, indicate that the site of action of the inhibitor is not on the initiation phase of protein synthesis but rather at a step after the binding of aminoacyl-tRNA to ribosomes. The increased inhibitor activity found in dystrophic muscle is discussed.

Protein synthesis in muscles from normal and dystrophic hamsters

“…However, cell-free preparations of muscle of dystrophic mice were reported to exhibit an increase in ribosomal activity together with a decrease in the labelling of myosin in polyribosomes translating the mRNA for this protein (Nwagwu, 1975;Srivastava, 1972). In our laboratory a proteinaceous inhibitor of peptide elongation was purified from the postmicrosomal-supernatant fraction of the muscle of dystrophic mice and accounted for a marked decrease in the capacity of cell-free preparations to carry out the elongation of peptides (Petryshyn & Nicholls, 1976;Petryshyn, 1977;Petryshyn & Nicholls, 1978).…”