Loveless M O, Kohlhepp S J, Gilbert D N
J Lab Clin Med. 1984 Feb;103(2):294-303.
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.
关于氨基糖苷类抗生素对高等真核生物核糖体影响的研究较少。为此，从大鼠肝脏中制备了细胞质核糖体。在体外，研究了在有和没有选定氨基糖苷类抗生素存在的情况下，聚（U）指导的核糖体蛋白质合成。还评估了聚（U）的错读情况。与早期使用不同核糖体来源的研究一致，巴龙霉素抑制无细胞蛋白质合成并导致聚（U）错读。与其他关于真核生物无细胞核糖体的研究结果相反，奈替米星、妥布霉素和新霉素在抑制蛋白质合成方面最为活跃，庆大霉素C2和新霉素导致明显的错读。因此，先前关于巴龙胺片段（存在于巴龙霉素中）可能是体外抑制蛋白质合成和错读的结构要求的建议，并未得到大鼠肝脏核糖体实验结果的证实。市售庆大霉素C是庆大霉素C1、C1a和C2的混合物。尽管化学结构几乎相同，但这三种成分在诱导聚（U）错读方面表现出极大的差异。C2最活跃，其次是C1a。总之，选定的氨基糖苷类抗生素在由大鼠肝脏制备的体外核糖体系统中导致聚（U）信使的抑制和错译。这些影响并不局限于含巴龙胺的氨基糖苷类抗生素。庆大霉素C2比庆大霉素C复合物的其他两种成分导致更多的聚（U）错读。
