High Error Rates in Selenocysteine Insertion in Mammalian Cells Treated with the Antibiotic Doxycycline, Chloramphenicol, or Geneticinстатья
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Дата последнего поиска статьи во внешних источниках: 6 декабря 2018 г.
Аннотация:Antibiotics cause errors in bacterial translation, but their effects on translation in mammalian cells are less well characterized. We found that doxycycline (Dox), chloramphenicol (Cp) and geneticin (G418) interfered with insertion of selenocysteine (Sec), which is encoded by the stop codon, UGA, into selenoproteins in murine EMT6 cells. Treatment of EMT6 cells with these antibiotics reduced enzymatic activities and Sec insertion into thioredoxin reductase 1 (TR1) and glutathione peroxidase 1 (GPx1), but differentially affected the levels of these proteins due to varying errors in Sec insertion at UGA. In the presence of Dox, Cp or G418, the Sec-containing form of TR1 decreased, whereas the arginine-containing and truncated forms of this protein increased. We also detected selenoprotein- and antibiotic-specific misinsertion of cysteine and tryptophan. Furthermore, misinsertion of arginine in place of Sec was commonly observed in GPx1 and glutathione peroxidase 4. TR1 was the most and GPx1 the least affected by these translation errors, consistent with the differential use of two Sec tRNA isoforms and their distinct roles in supporting accuracy of Sec insertion into selenoproteins. The data reveal widespread errors in inserting Sec into proteins and in dysregulation of selenoprotein expression and function upon antibiotic treatment.