Archives of toxicology, 2017-11, Vol.91 (11), p.3507-3516
2017
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- Autor(en) / Beteiligte
- Titel
- Arsenic-mediated hyperpigmentation in skin via NF-kappa B/endothelin-1 signaling in an originally developed hairless mouse model
- Ist Teil von
- Archives of toxicology, 2017-11, Vol.91 (11), p.3507-3516
- Ort / Verlag
- Berlin/Heidelberg: Springer Berlin Heidelberg
- Erscheinungsjahr
- 2017
- Quelle
- SpringerLink
- Beschreibungen/Notizen
- Chronic exposure to arsenic is associated with various diseases in humans. Skin hyperpigmentation is the most sensitive objective symptom for patients with arsenicosis. However, there is very limited information about the mechanism of arsenic-mediated skin hyperpigmentation in vivo. In this study, hairless homozygous mice ( Hr/Hr -mice) that drank water containing 3 and 30 µM arsenic for 2 months developed skin hyperpigmentation with increased levels of arsenic and number of melanocytes in the skin. Since it is possible for humans to be exposed to 3 µM of arsenic in well drinking water, our results suggest that the Hr/Hr -mice could be a novel model sensitively reflecting arsenic-mediated skin hyperpigmentation. We then analyzed the mechanism of arsenic-mediated skin hyperpigmentation. The epidermis of Hr/Hr -mice and human HaCaT skin keratinocytes exposed to arsenic for 2 and 4 months, respectively, showed 5.4–21.5-fold increased levels of endothelin-1 (ET-1) expression via NF-kappa B activation. Coexposure of primary normal human epithelial melanocytes to arsenic and ET-1 activated their proliferation and melanin synthesis with increased levels of MITF-M and ET-1 receptor expression. Our results suggest that interaction between keratinocytes and melanocytes in the skin through ET-1 and its receptor contributes to arsenic-mediated skin pigmentation, a hallmark of arsenicosis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0340-5761eISSN: 1432-0738DOI: 10.1007/s00204-017-1975-0Titel-ID: cdi_proquest_miscellaneous_1895276581
- Format
- –
- Schlagworte
- Animals, Arsenic, Arsenic - toxicity, Bioaccumulation, Biomedical and Life Sciences, Biomedicine, Cell Line, Chronic exposure, Disease Models, Animal, Drinking water, Drinking Water - adverse effects, Endothelin 1, Endothelin-1 - metabolism, Environmental Health, Epidermis, Epidermis - cytology, Epidermis - drug effects, Epidermis - metabolism, Exposure, Hairless, Homozygote, Humans, Hyperpigmentation, Hyperpigmentation - chemically induced, Hyperpigmentation - metabolism, In vivo methods and tests, Inorganic Compounds, Keratinocytes, Keratinocytes - drug effects, Keratinocytes - metabolism, Keratinocytes - pathology, Melanin, Melanocytes, Melanocytes - drug effects, Melanocytes - metabolism, Mice, Mice, Hairless, Microphthalmia-associated transcription factor, NF-kappa B - metabolism, NF-κB protein, Occupational Medicine/Industrial Medicine, Pharmacology/Toxicology, Pigmentation, Receptor, Endothelin B - genetics, Receptor, Endothelin B - metabolism, Signaling, Skin diseases, Skin pigmentation, Toxicity