dc.contributor.author
Renko, Kostja
dc.contributor.author
Martitz, Janine
dc.contributor.author
Hybsier, Sandra
dc.contributor.author
Heynisch, Bjoern
dc.contributor.author
Voss, Linn
dc.contributor.author
Everley, Robert A.
dc.contributor.author
Gygi, Steven P.
dc.contributor.author
Stoedter, Mette
dc.contributor.author
Wisniewska, Monika
dc.contributor.author
Köhrle, Josef
dc.contributor.author
Gladyshev, Vadim N.
dc.contributor.author
Schomburg, Lutz
dc.date.accessioned
2018-06-08T10:48:50Z
dc.date.available
2017-09-01T11:42:46.960Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/21134
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-24431
dc.description.abstract
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.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Selenium-binding proteins
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Scientific Reports. - 7 (2017), Artikel Nr. 4391
dcterms.bibliographicCitation.doi
10.1038/s41598-017-04586-9
dcterms.bibliographicCitation.url
http://www.nature.com/articles/s41598-017-04586-9
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000027768
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008687
dcterms.accessRights.openaire
open access