Abstract:
AIMS:We have tested the hypothesis that selenium (Se)-containing antioxidative enzymes protect thyroid epithelial cells from oxidative damage associated with enzymatic production of hydrogen peroxide required for thyroid hormone biosynthesis. Thyroid epithelial cells therefore express antioxidative enzymes, including catalase, peroxiredoxins, thioredoxin reductases, and glutathione peroxidases (GPxs). The latter two enzyme families contain highly active peroxide-degrading enzymes that carry selenocysteine (Sec) in their active centers. Since low Se status has been associated with thyroid disorders, selenoproteins are considered essential for thyroid integrity and function. We have conditionally inactivated selenoprotein biosynthesis in thyrocytes by targeting Sec tRNA. RESULTS:Constitutive and inducible Cre/loxP-mediated recombination of tRNA([Ser]Sec) drastically reduced activities of selenoenzymes GPx and type I-deiodinase in thyroid extracts. Immunohistochemical staining revealed increased 4-hydroxynonenal and 3-nitro-tyrosine levels consistent with increased oxidative stress. However, gross thyroid morphology remained intact for at least 6 months after recombination. Circulating thyroid hormone levels remained normal in mutant mice, while thyrotropin (TSH) levels were moderately elevated. Challenging mutant mice with low iodine diet increased TSH, but did not lead to destruction of selenoprotein-deficient thyroids. INNOVATION:This is the first report probing the assumed physiological roles of selenoproteins in the thyroid using a genetic loss-of-function approach. CONCLUSION:We conclude that selenoproteins protect thyrocytes from oxidative damage and modulate thyroid hormone biosynthesis, but are not essential for thyrocyte survival.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Chiu-Ugalde J,Wirth EK,Klein MO,Sapin R,Fradejas-Villar N,Renko K,Schomburg L,Köhrle J,Schweizer Udoi
10.1089/ars.2011.4055subject
Has Abstractpub_date
2012-09-15 00:00:00pages
902-13issue
6eissn
1523-0864issn
1557-7716journal_volume
17pub_type
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journal_title:Antioxidants & redox signaling
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journal_title:Antioxidants & redox signaling
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journal_title:Antioxidants & redox signaling
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