Topical Drug Rescue Strategy and Skin Protection Based on the Role of Mc1r in Uv-induced Tanning.
From: Melanoma Program, Dana-Farber Cancer Institute & Children’s Hospital, 44 Binney Street, Boston, Massachusetts 02115, USA.
Nature
- Publish Date: Sep 2006
- ISSN: 1476-4687
- Volume: 443
- Issue: 7109
- Pages: 340-4
- Medium: Internet
- Language: English
- Citation (JAMA): D'Orazio John A, Nobuhisa Tetsuji, Cui Rutao, et al. Topical Drug Rescue Strategy and Skin Protection Based on the Role of Mc1r in Uv-induced Tanning.. Nature Sep 2006;443:340-4
Abstract
Ultraviolet-light (UV)-induced tanning is defective in numerous ‘fair-skinned’ individuals, many of whom contain functional disruption of the melanocortin 1 receptor (MC1R). Although this suggested a critical role for the MC1R ligand melanocyte stimulating hormone (MSH) in this response, a genetically controlled system has been lacking in which to determine the precise role of MSH-MC1R. Here we show that ultraviolet light potently induces expression of MSH in keratinocytes, but fails to stimulate pigmentation in the absence of functional MC1R in red/blonde-haired Mc1r(e/e) mice. However, pigmentation could be rescued by topical application of the cyclic AMP agonist forskolin, without the need for ultraviolet light, demonstrating that the pigmentation machinery is available despite the absence of functional MC1R. This chemically induced pigmentation was protective against ultraviolet-light-induced cutaneous DNA damage and tumorigenesis when tested in the cancer-prone, xeroderma-pigmentosum-complementation-group-C-deficient genetic background. These data emphasize the essential role of intercellular MSH signalling in the tanning response, and suggest a clinical strategy for topical small-molecule manipulation of pigmentation.
Mesh Headings (Keywords): Administration, Topical, Animals, Forskolin, Melanins, Melanocyte-Stimulating Hormones, Mice, Mice, Inbred C57BL, Receptor, Melanocortin, Type 1, Signal Transduction, Skin, Skin Diseases, Skin Pigmentation, Ultraviolet Rays
Check for Full Text / PubMed Unique Identifier (PMID): 16988713
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