MECHANISM OF ACTION OF NEOTHRAMYCIN
MECHANISM OF ACTION OF NEOTHRAMYCIN
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新霉素的作用机制
DOI：
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发表时间：
1978
期刊：
影响因子：
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通讯作者：
N. Tanaka
中科院分区：
文献类型：
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作者：
I. Maruyama;Hideo Suzuki;N. Tanaka
新霉素在0.5-1.0μg/ml浓度下可抑制小鼠淋巴母细胞瘤L5178Y和HeLa细胞的生长，在5.0μg/ml浓度下表现出致死作用。浓度为 37 μg/ml 时发现对大肠杆菌的生长有大约 50% 的抑制作用。研究了新霉素对哺乳动物和细菌细胞中大分子合成的影响。在淋巴母细胞瘤 L5178Y 的完整细胞中，抗生素优先抑制 RNA 而非 DNA 合成：即在抗生素浓度为 1.4 μg/ml 时观察到前者约 50% 的抑制，而在 12.0 μg/ml 时观察到后者的抑制约 50%。蛋白质合成没有受到显着影响。与哺乳动物细胞中的效果相反，在大肠杆菌的完整细胞中，抗生素对胸腺嘧啶摄取到 DNA 的阻断比尿苷掺入 RNA 的阻断更明显。然而，观察到新霉素会引起 DNA 的显着降解，并且胸腺嘧啶摄取的明显抑制似乎是由于 DNA 的降解，而不是由于 DNA 净合成的抑制。在大肠杆菌中，抗生素对 RNA 合成的抑制作用比对哺乳动物细胞中 DNA 合成的抑制作用更大。新霉素不会显着影响经甲苯处理的大肠杆菌 polA- 细胞的 DNA 合成，而同一系统的 RNA 合成则被抗生素显着阻断。使用大肠杆菌酶和小牛胸腺 DNA 作为模板，新霉素被证明可以防止 DNA 依赖性 RNA 和 DNA 聚合酶反应。 RNA 聚合酶反应比 DNA 聚合酶 I 受到更严重的抑制：即在抗生素浓度为 11 μg/ml 时观察到对 RNA 聚合酶反应的抑制约 50%，而在 100 μg/ml 时观察到 DNA 聚合酶 I 的抑制。 DNA 聚合酶 I 的抑制程度随着模板 DNA 浓度的增加而逆转，但酶的浓度却没有逆转，这表明抗生素与 DNA 存在直接相互作用。聚合酶反应的抑制程度取决于模板DNA和新霉素的预孵育时间，逐渐增加直至预孵育达到60分钟。这表明DNA与抗生素的相互作用可能需要一定的时间。
Neothramycin was observed to prevent growth of mouse lymphoblastoma L5178Y and HeLa cells at the concentration of 0.5-1.0μg/ml and exhibited a lethal effect at 5.0μg/ml. Approximately 50% growth inhibition of E. coli was found at the concentration of 37 μg/ml. The effect of neothramycin on macromolecular syntheses in the mammalian and bacterial cells was investigated. The antibiotic produced a preferential inhibition of RNA over DNA synthesis in the intact cells of lymphoblastoma L5178Y: i.e. approximately 50% inhibition of the former was observed at the antibiotic concentration of 1.4 μg/ml, and that of the latter at 12.0μg/ml. Protein synthesis was not significantly affected. Contrary to the effect in the mammalian cells, thymine uptake into DNA was more markedly blocked than uridine incorporation into RNA by the antibiotic in the intact cells of E. coli. However, neothramycin was observed to cause a significant degradation of DNA, and the apparent inhibition of thymine uptake seemed to be due to degradation of DNA but not to the inhibition of net DNA synthesis. In E. coli the antibiotic prevented RNA synthesis more profoundly than DNA synthesis as in the mammalian cells. DNA synthesis with toluene-treated cells of E. coli polA- was not significantly affected by neothramycin, while RNA synthesis with the same system was markedly blocked by the antibiotic. Neothramycin was demonstrated to prevent DNA-dependent RNA and DNA polymerase reactions, using E. coli enzymes and calf thymus DNA as a template. RNA polymerase reaction was more profoundly inhibited than DNA polymerase I: i.e. approximately 50% inhibition of RNA polymerase reaction was observed at the antibiotic concentration of 11 μg/ml, and that of DNA polymerase I at 100 μg/ml. The inhibition degree of DNA polymerase I was reversed by the increasing concentration of template DNA but not by that of the enzyme, suggesting the direct interaction of the antibiotic with DNA. The degree of inhibition of the polymerase reactions depended upon the period of preincubation of template DNA and neothramycin, increasing gradually until the preincubation reached 60 minutes. It suggested that the interaction of DNA and the antibiotic might need a certain time.