Aminoglycosides Decrease Glutathione Peroxidase-1 Activity by Interfering with Selenocysteine Incorporation.
From: Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. dhandy@rics.bwh.harvard.edu
The Journal of biological chemistry
- Publish Date: Feb 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 6
- Pages: 3382-8
- Medium: Print
- Language: English
- Citation (JAMA): Handy Diane E, Hang Gaozhen, Scolaro John, et al. Aminoglycosides Decrease Glutathione Peroxidase-1 Activity by Interfering with Selenocysteine Incorporation.. J. Biol. Chem. Feb 2006;281:3382-8
Abstract
Cellular glutathione peroxidase is a key intracellular antioxidant enzyme that contains a selenocysteine residue at its active site. Selenium, a selenocysteine incorporation sequence in the 3’-untranslated region of the glutathione peroxidase mRNA, and other translational cofactors are necessary for “read-through” of a UGA stop codon that specifies selenocysteine incorporation. Aminoglycoside antibiotics facilitate read-through of premature stop codons in prokayotes and eukaryotes. We studied the effects of G418, an aminoglycoside, on cellular glutathione peroxidase expression and function in mammalian cells. Insertion of a selenocysteine incorporation element along with a UGA codon into a reporter construct allows for read-through only in the presence of selenium. G418 increased read-through in selenium-replete cells as well as in the absence of selenium. G418 treatment increased immunodetectable endogenous or recombinant glutathione peroxidase but reduced the specific activity of the enzyme. Tandem mass spectrometry experiments indicated that G418 caused a substitution of l-arginine for selenocysteine. These data show that G418 can affect the biosynthesis of this key antioxidant enzyme by promoting substitution at the UGA codon.
Mesh Headings (Keywords): 3’ Untranslated Regions, Amebicides, Aminoglycosides, Animals, Antioxidants, Aorta, Arginine, Blotting, Western, COS Cells, Cattle, Cercopithecus aethiops, Cloning, Molecular, Codon, Codon, Terminator, DNA, Complementary, Dose-Response Relationship, Drug, Endothelial Cells, Genes, Reporter, Genetic Vectors, Glutathione Peroxidase, Humans, Luciferases, Mass Spectrometry, Mutation, Protein Biosynthesis, RNA, Messenger, Recombinant Proteins, Selenium, Selenocysteine, Selenoproteins, Transfection
Check for Full Text / PubMed Unique Identifier (PMID): 16354666
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.