Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P

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 (S...

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Autores principales:	Kostja Renko, Janine Martitz, Sandra Hybsier, Bjoern Heynisch, Linn Voss, Robert A. Everley, Steven P. Gygi, Mette Stoedter, Monika Wisniewska, Josef Köhrle, Vadim N. Gladyshev, Lutz Schomburg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/53c13c6cf1a34777988a908974caa136
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spelling	oai:doaj.org-article:53c13c6cf1a34777988a908974caa1362021-12-02T11:41:12ZAminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P10.1038/s41598-017-04586-92045-2322https://doaj.org/article/53c13c6cf1a34777988a908974caa1362017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04586-9https://doaj.org/toc/2045-2322Abstract 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.Kostja RenkoJanine MartitzSandra HybsierBjoern HeynischLinn VossRobert A. EverleySteven P. GygiMette StoedterMonika WisniewskaJosef KöhrleVadim N. GladyshevLutz SchomburgNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kostja Renko Janine Martitz Sandra Hybsier Bjoern Heynisch Linn Voss Robert A. Everley Steven P. Gygi Mette Stoedter Monika Wisniewska Josef Köhrle Vadim N. Gladyshev Lutz Schomburg Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P
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.
format	article
author	Kostja Renko Janine Martitz Sandra Hybsier Bjoern Heynisch Linn Voss Robert A. Everley Steven P. Gygi Mette Stoedter Monika Wisniewska Josef Köhrle Vadim N. Gladyshev Lutz Schomburg
author_facet	Kostja Renko Janine Martitz Sandra Hybsier Bjoern Heynisch Linn Voss Robert A. Everley Steven P. Gygi Mette Stoedter Monika Wisniewska Josef Köhrle Vadim N. Gladyshev Lutz Schomburg
author_sort	Kostja Renko
title	Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P
title_short	Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P
title_full	Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P
title_fullStr	Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P
title_full_unstemmed	Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P
title_sort	aminoglycoside-driven biosynthesis of selenium-deficient selenoprotein p
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/53c13c6cf1a34777988a908974caa136
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Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P

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