Menth Marianne, Schmutzler Cornelia, Mentrup Birgit, Hoang-Vu Cuong, Takahashi Kazuhiko, Honjoh Tsutomu, Köhrle Josef
Abteilung für Molekulare Innere Medizin und Klinische Forschergruppe der Medizinischen Poliklinik, Universität Würzburg, Würzburg, Germany.
Thyroid. 2005 May;15(5):405-16. doi: 10.1089/thy.2005.15.405.
Hürthle cell carcinomas (HTC) are characterized by mitochondrial amplification and enhanced oxygen metabolism. To clarify if defects in enzymes scavenging reactive oxygen species are involved in the pathogenesis of HTC, we analyzed selenium (Se)-dependent expression of various detoxifying selenoproteins in the HTC cell line XTC.UC1. Glutathione peroxidase and thioredoxin reductase activity was found both in cell lysates and conditioned media of XTC.UC1 cells and was increased by Na(2)SeO(3). Western blot analysis demonstrated the presence of thioredoxin reductase both in cell lysates and conditioned media and of glutathione peroxidase 3 in conditioned media. Type I 5'-deiodinase, another selenoprotein that catalyzes thyroid hormone metabolism, was detectable only in cell lysates by enzyme assay and Western blot, and responded to stimulation by both Na(2)SeO(3) and retinoic acid. A selenoprotein P signal was detected in conditioned media by Western blot, but was not enhanced by Na(2)SeO(3) treatment. In situ hybridization revealed glutathione peroxidase mRNAs in HTC specimen; glutathione peroxidase 3 mRNA levels were reduced. These data suggest adequate expression and Se-dependent regulation of a couple of selenoproteins involved in antioxidant defense and thyroid hormone metabolism in XTC.UC1 cells, so far giving no evidence of a role of these proteins in the pathogenesis of HTCs.
许特莱细胞癌（HTC）的特征是线粒体扩增和氧代谢增强。为了阐明清除活性氧的酶缺陷是否参与HTC的发病机制，我们分析了HTC细胞系XTC.UC1中各种解毒硒蛋白的硒（Se）依赖性表达。在XTC.UC1细胞的细胞裂解物和条件培养基中均发现了谷胱甘肽过氧化物酶和硫氧还蛋白还原酶活性，并且Na₂SeO₃可使其增加。蛋白质印迹分析表明，细胞裂解物和条件培养基中均存在硫氧还蛋白还原酶，条件培养基中存在谷胱甘肽过氧化物酶3。I型5'-脱碘酶是另一种催化甲状腺激素代谢的硒蛋白，仅通过酶测定和蛋白质印迹在细胞裂解物中可检测到，并且对Na₂SeO₃和视黄酸的刺激均有反应。通过蛋白质印迹在条件培养基中检测到硒蛋白P信号，但Na₂SeO₃处理并未增强该信号。原位杂交显示HTC标本中有谷胱甘肽过氧化物酶mRNA；谷胱甘肽过氧化物酶3 mRNA水平降低。这些数据表明，XTC.UC1细胞中参与抗氧化防御和甲状腺激素代谢的几种硒蛋白有充分的表达和硒依赖性调节，目前尚无证据表明这些蛋白在HTC发病机制中起作用。
