Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P
| العنوان: | Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P |
|---|---|
| المؤلفون: | Steven P. Gygi, Josef Köhrle, Kostja Renko, Mette Stoedter, Vadim N. Gladyshev, Janine Martitz, Linn Voss, Lutz Schomburg, Sandra Hybsier, Robert A. Everley, Bjoern Heynisch, Monika Wisniewska |
| المصدر: | Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) Scientific Reports |
| بيانات النشر: | Freie Universität Berlin, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, GPX1, GPX2, SEPP1, Science, Gene Expression, Biology, Article, Mice, Selenium, 03 medical and health sciences, chemistry.chemical_compound, Tandem Mass Spectrometry, Selenium deficiency, Cell Line, Tumor, Selenoprotein P, medicine, Animals, Humans, Amino Acids, chemistry.chemical_classification, Multidisciplinary, 030102 biochemistry & molecular biology, Selenocysteine, medicine.disease, Selenium-binding proteins, 3. Good health, Aminoglycosides, 030104 developmental biology, chemistry, Biochemistry, Protein Biosynthesis, Codon, Terminator, biology.protein, Hepatocytes, Medicine, Selenoprotein, Gentamicins, Chromatography, Liquid, Peroxidase |
| الوصف: | Selenoprotein biosynthesis relies on the co-translational insertion of selenocysteine in response to UGA codons. Aminoglycoside antibiotics interfere with ribosomal function and may cause codon misreading. We hypothesized that biosynthesis of the selenium (Se) transporter selenoprotein P (SELENOP) is particularly sensitive to antibiotics due to its ten in frame UGA codons. As liver regulates Se metabolism, we tested the aminoglycosides G418 and gentamicin in hepatoma cell lines (HepG2, Hep3B and Hepa1-6) and in experimental mice. In vitro, SELENOP levels increased strongly in response to G418, whereas expression of the glutathione peroxidases GPX1 and GPX2 was marginally affected. Se content of G418-induced SELENOP was dependent on Se availability, and was completely suppressed by G418 under Se-poor conditions. Selenocysteine residues were replaced mainly by cysteine, tryptophan and arginine in a codon-specific manner. Interestingly, in young healthy mice, antibiotic treatment failed to affect Selenop biosynthesis to a detectable degree. These findings suggest that the interfering activity of aminoglycosides on selenoprotein biosynthesis can be severe, but depend on the Se status, and other parameters likely including age and general health. Focused analyses with aminoglycoside-treated patients are needed next to evaluate a possible interference of selenoprotein biosynthesis by the antibiotics and elucidate potential side effects. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53079d7421ac51e3bbd6d3b44a440cce https://refubium.fu-berlin.de/handle/fub188/21134 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....53079d7421ac51e3bbd6d3b44a440cce |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |