Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones
Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones
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DOI：
10.1128/aac.01411-05
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发表时间：
2006-06-01
影响因子：
4.9
通讯作者：
Marks, TA
中科院分区：
文献类型：
--
作者：
McKee, EE;Ferguson, M;Marks, TA
在从大鼠心脏和肝脏以及兔心脏和骨髓中分离的完整线粒体中测定了具有不同抗菌效力的各种恶唑烷酮（包括利奈唑胺）对线粒体蛋白合成的影响。结果表明，恶唑烷酮类抗生素的一般特征是抑制哺乳动物线粒体蛋白质合成。在研究的所有组织的线粒体中，抑制作用相似。此外，作为抗生素非常有效的恶唑烷酮在抑制线粒体蛋白质合成方面一致有效。将这些结果与通过抑制细菌蛋白质合成发挥作用的其他抗生素的抑制谱进行比较。其中，氯霉素和四环素是哺乳动物线粒体蛋白质合成的显著抑制剂，而大环内酯类、林可酰胺类和氨基糖苷类则不是。未来开发恶唑烷酮类抗生素必须评估潜在的线粒体毒性。
The effects of a variety of oxazolidinones, with different antibacterial potencies, including linezolid, on mitochondrial protein synthesis were determined in intact mitochondria isolated from rat heart and liver and rabbit heart and bone marrow. The results demonstrate that a general feature of the oxazolidinone class of antibiotics is the inhibition of mammalian mitochondrial protein synthesis. Inhibition was similar in mitochondria from all tissues studied. Further, oxazolidinones that were very potent as antibiotics were uniformly potent in inhibiting mitochondrial protein synthesis. These results were compared to the inhibitory profiles of other antibiotics that function by inhibiting bacterial protein synthesis. Of these, chloramphenicol and tetracycline were significant inhibitors of mammalian mitochondrial protein synthesis while the macrolides, lincosamides, and aminoglycosides were not. Development of future antibiotics from the oxazolidinone class will have to evaluate potential mitochondrial toxicity.