Selenoproteins are essential for proper keratinocyte function and skin development.
Selenoproteins are essential for proper keratinocyte function and skin development.
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DOI：
10.1371/journal.pone.0012249
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发表时间：
2010-08-18
期刊：
影响因子：
3.7
通讯作者：
Hatfield DL
中科院分区：
文献类型：
--
作者：
Sengupta A;Lichti UF;Carlson BA;Ryscavage AO;Gladyshev VN;Yuspa SH;Hatfield DL
已知膳食硒可保护皮肤免受紫外线诱导的损伤和癌症，其局部应用可改善人类皮肤表面参数，而硒缺乏会损害皮肤中的保护性抗氧化酶。此外，人类和啮齿动物的皮肤和毛发异常可能是由硒缺乏引起的，这可以通过膳食硒补充剂来克服。硒最重要的生物学功能归因于硒蛋白，即以氨基酸硒代半胱氨酸（Sec）形式含有硒的蛋白质。Sec插入蛋白质依赖于Sec tRNA;因此，敲除Sec tRNA基因（Trsp）会消除硒蛋白的表达。我们产生了有针对性地去除角蛋白14（K14）表达细胞及其分化后代中的硒蛋白的小鼠。基因敲除的后代有一个矮小的表型，发展皮肤异常，并经历了过早死亡。表皮细胞中硒蛋白的缺乏导致表皮增生和毛囊形态发生异常，并伴有出生后进行性脱发。进一步的分析表明，硒蛋白是皮肤中必不可少的抗氧化剂，并揭示了它们在角质形成细胞生长和活力中的作用。这项研究将严重的硒蛋白缺乏与皮肤和毛发异常联系起来，并为这些蛋白质在角质形成细胞功能和皮肤发育中的作用提供了遗传学证据。
Dietary selenium is known to protect skin against UV-induced damage and cancer and its topical application improves skin surface parameters in humans, while selenium deficiency compromises protective antioxidant enzymes in skin. Furthermore, skin and hair abnormalities in humans and rodents may be caused by selenium deficiency, which are overcome by dietary selenium supplementation. Most important biological functions of selenium are attributed to selenoproteins, proteins containing selenium in the form of the amino acid, selenocysteine (Sec). Sec insertion into proteins depends on Sec tRNA; thus, knocking out the Sec tRNA gene (Trsp) ablates selenoprotein expression. We generated mice with targeted removal of selenoproteins in keratin 14 (K14) expressing cells and their differentiated descendents. The knockout progeny had a runt phenotype, developed skin abnormalities and experienced premature death. Lack of selenoproteins in epidermal cells led to the development of hyperplastic epidermis and aberrant hair follicle morphogenesis, accompanied by progressive alopecia after birth. Further analyses revealed that selenoproteins are essential antioxidants in skin and unveiled their role in keratinocyte growth and viability. This study links severe selenoprotein deficiency to abnormalities in skin and hair and provides genetic evidence for the role of these proteins in keratinocyte function and cutaneous development.
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影响因子：
7.1
作者：
Berger, Mette M.;Binnert, Christophe;Tappy, Luc
通讯作者：
Tappy, Luc
人角蛋白：生物学和病理学。
影响因子：
2.3
作者：
Moll, Roland;Divo, Markus;Langbein, Lutz
通讯作者：
Langbein, Lutz
影响因子：
56.9
作者：
Kryukov, GV;Castellano, S;Gladyshev, VN
通讯作者：
Gladyshev, VN
影响因子：
4.1
作者：
Kanekura, T;Yotsumoto, S;Kanzaki, T
通讯作者：
Kanzaki, T
影响因子：
30.8
作者：
Jonkers, J;Meuwissen, R;Berns, A
通讯作者：
Berns, A