Thyroid Function Is Maintained Despite Increased Oxidative Stress in Mice Lacking Selenoprotein Biosynthesis in Thyroid Epithelial Cells
Thyroid Function Is Maintained Despite Increased Oxidative Stress in Mice Lacking Selenoprotein Biosynthesis in Thyroid Epithelial Cells
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DOI：
10.1089/ars.2011.4055
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发表时间：
2012-09-01
影响因子：
6.6
通讯作者：
Schweizer, Ulrich
中科院分区：
文献类型：
--
作者：
Chiu-Ugalde, Jazmin;Wirth, Eva K.;Schweizer, Ulrich
目的：我们已经测试的假设，含硒（Se）的抗氧化酶保护甲状腺上皮细胞的氧化损伤与酶促生产的过氧化氢所需的甲状腺激素的生物合成。因此，甲状腺上皮细胞表达抗氧化酶，包括过氧化氢酶、过氧化物酶、硫氧还蛋白还原酶和谷胱甘肽过氧化物酶（GPx）。后两个酶家族含有高活性的过氧化物降解酶，其活性中心携带硒代半胱氨酸（Sec）。由于低硒状态与甲状腺疾病有关，硒蛋白被认为是甲状腺完整性和功能所必需的。我们有条件地失活硒蛋白的合成在甲状腺细胞靶向Sec tRNA。结果如下：组成型和诱导型Cre/loxP介导的tRNA重组（[Ser]Sec）大大降低了甲状腺提取物中硒酶GPx和I型脱碘酶的活性。免疫组织化学染色显示4-羟基壬烯醛和3-硝基酪氨酸水平增加与氧化应激增加一致。然而，大体甲状腺形态在重组后至少6个月内保持完整。突变小鼠的循环甲状腺激素水平保持正常，而促甲状腺激素（TSH）水平中度升高。用低碘饮食喂养突变小鼠可增加TSH，但不会导致硒蛋白缺乏甲状腺的破坏。创新：这是第一份报告探讨假定的生理作用的硒蛋白在甲状腺中使用的遗传功能丧失的方法。结论：我们的结论是，硒蛋白保护甲状腺细胞免受氧化损伤和调节甲状腺激素的生物合成，但不是甲状腺细胞的生存所必需的。抗氧化剂。氧化还原信号。17，902-913。
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. Antioxid. Redox Signal. 17, 902-913.