Abstract
Abstract When Sarcoma 37 ascites cells were incubated in the presence of actinomycin D, protein synthesis was inhibited. The inhibitory effect could be prevented or relieved by glucose or by a variety of glycolyzable substrates. The inhibitory effect was independent of the concentration of the labeled amino acid precursor. Under conditions inhibitory to protein synthesis, no significant inhibition of respiration or of amino acid uptake was observed. Actinomycin D inhibited amino acid incorporation into ribosomal and soluble protein, as well as into soluble ribonucleic acid, and these inhibitory effects were all abolished by the presence of glucose. Three analogues of actinomycin D, which were inactive as inhibitors of RNA synthesis, were inactive as inhibitors of protein synthesis in the present studies. Actinomycin D also inhibited the incorporation of mevalonic acid into sterols, and the inhibition was relieved by glucose. Although the characteristics of these inhibitions suggested an interference with the availability of oxidative energy, measurements of levels of adenine nucleotides and of incorporation of 32P-labeled orthophosphate into ATP failed to show an effect of the antibiotic on oxidative phosphorylation.
Highlights
When Sarcoma 37 ascites cells were incubated in the presence of actinomycin D, protein synthesis was inhibited
Actinomycin D inhibited amino acid incorporation into ribosomal and soluble protein, as well as into soluble ribonucleic acid, and these inhibitory effects were all abolished by the presence of glucose
Actinomycin D inhibited the incorporation of mevalonic acid into sterols, and the inhibition was relieved by glucose
Summary
When Sarcoma 37 ascites cells were incubated in the presence of actinomycin D, protein synthesis was inhibited. Since the antibiotic is a potent inhibitor of ribonucleic acid production [4], the effect on protein synthesis has been attributed principally to a block in production of labile template RNA which must be continuously replenished for protein synthesis to be maintained It was found [5] that actinomycin D inhibited protein synthesis in vitro in Sarcoma 37 ascites cells, but the inhibitory effect could be prevented or relieved by addition of glucose to the incubation medium, indicating that the inhibition was not related to turnover of a template RNA.
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