Selenoproteins are essential for proper keratinocyte function and skin development.
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.
Sengupta
Aniruddha
A
Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Lichti
Ulrike F
UF
Carlson
Bradley A
BA
Ryscavage
Andrew O
AO
Gladyshev
Vadim N
VN
Yuspa
Stuart H
SH
Hatfield
Dolph L
DL
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D015227:Lipid Peroxidation; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011995:Recombination, Genetic; D012643:Selenium / Q000172:deficiency; D051140:Selenoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*
D000975:Antioxidants; D015415:Biomarkers; D053547:Keratin-14; D012333:RNA, Messenger; D012345:RNA, Transfer, Amino Acid-Specific; D017382:Reactive Oxygen Species; D051140:Selenoproteins; C036928:tRNA, selenocysteine-; D012643:Selenium
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