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The effects of dioxin action on hr-deficient epidermal keratinocytes are associated with changes in expression of AhR-regulated genesстатья Тезисы
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 19 декабря 2019 г.
- Авторы: Rudyak S.G., Shinin V.V., Usakin L.A., Belushkina N.N., Paltsev M.A., Letters Panteleyev A.A.
- Журнал: Toxicology Letters
- Том: 295
- Номер: Suppl 1
- Год издания: 2018
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: S242
- Последняя страница: S243
- DOI: 10.1016/j.toxlet.2018.06.1005
- Аннотация: Hairless mice, bearing a mutation in hr gene, have an increased skin sensitivity to the ligand of aryl-hydrocarbon receptor (AhR), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These specific effects of TCDD action are manifested in severe chloracne-like cutaneous lesions and skin carcinomas, lacking in wild type mice. Hairless gene (hr) encodes histone demethylase, which is highly expressed in epidermal compartment of the skin, but missing from most other tissues. It was suggested that hr enzyme is involved in regulation of gene silencing in keratinocytes, although its immediate targets remain unknown. We have used hairless mice and keratinocyte cultures obtained from the skin of hairless and wild-type animals to determine the range of TCDD-induced skin effects in hr/wt backgrounds. 1.6 ug of TCDD were applied to skin of hairless mice for 25 days, while hr and wt keratinocyte cell cultures were treated with 0–100 nm TCDD and its non-toxic analogue 6-Formylindolo[3,2-b]carbazole (FICZ). In hr mice, topical application of TCDD produced an increased skin inflammation, infiltration of neutrophils in the epidermis, involution of sebaceous glands, and changes in localization of keratinocyte differentiation markers. Concomitantly, treatment of hr/wt keratinocytes with TCDD/FICZ resulted in upregulation of AhR-regulated genes (Cyp1A1, etc.), with varying levels of induction between hairless and wild-type cells, and highly dependent on conditions and time of incubation. These results suggest that hr might be involved in regulation of AhR-dependent TCDD response and elucidate novel potential targets of hr- and TCDD-mediated gene regulation.
- Добавил в систему: Белушкина Наталья Николаевна