The influence of aminoglycoside antibiotics on the in vitro function of rat liver ribosomes.
There are few studies of the influence of aminoglycoside antibiotics on the ribosomes of higher eukaryotic organisms. To this end, cytoplasmic ribosomes were prepared from rat liver. In vitro, poly(U)-directed ribosome protein synthesis was studied in the presence and absence of selected aminoglycosides. Misreading of poly(U) was also assessed. Consistent with earlier studies using different sources of ribosomes, paromomycin inhibited cell-free protein synthesis and caused poly(U) misreading. In contrast to the findings of other studies in cell-free ribosomes of eukaryotic organisms, netilmicin, tobramycin, and neomycin were most active in inhibiting protein synthesis, and gentamicin C2 and neomycin caused appreciable misreading. Thus the previous suggestion that a paromamine fragment (found in paromomycin) might be a structural requirement for in vitro inhibition of protein synthesis and misreading is not substantiated by the results in rat liver ribosomes. Commercial gentamicin C is a mixture of gentamicins C1, C1a, and C2. Despite nearly identical chemical structures, the three constituents displayed greatly different propensities for inducing poly(U) misreading. C2 was the most active, followed by C1a. In summary, selected aminoglycoside antibiotics caused inhibition and mistranslation of poly(U) messenger in an in vitro ribosome system prepared from rat liver. These effects were not limited to paromamine-containing aminoglycoside antibiotics. Gentamicin C2 caused much more poly(U) misreading than the other two constituents of the gentamicin C complex.
D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010649:Phenylalanine / Q000378:metabolism; D011072:Poly U; D051381:Rats; D011916:Rats, Inbred F344; D012269:Ribosomal Proteins / Q000096:biosynthesis*; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012269:Ribosomal Proteins; D011072:Poly U; D010649:Phenylalanine; D007930:Leucine