Publication date: Aug 09, 2019
Homozygous loss of function of the melanocortin 1 receptor (MC1R) is associated with a pheomelanotic pigment phenotype and increased melanoma risk. MC1R heterozygosity is less well studied, although individuals inheriting one loss-of-function MC1R allele are also melanoma-prone. Using the K14-Scf C57BL/6J animal model whose skin is characterized by life-long retention of interfollicular epidermal melanocytes like that of the human, we studied pigmentary, UV responses and DNA repair capacity in the skin of variant Mc1r background. Topical application of forskolin, a skin-permeable pharmacologic activator of cAMP induction to mimic native Mc1r signaling, increased epidermal eumelanin levels, increased the capacity of Mc1r-heterozygous skin to resist UV-mediated inflammation, and enhanced the skin’s ability to clear UV photolesions from DNA. Interestingly, topical cAMP induction also promoted melanin accumulation, UV resistance, and accelerated clearance in Mc1r fully-intact skin. Together, our findings suggest that heterozygous Mc1r loss is associated with an intermediately melanized and DNA repair-proficient epidermal phenotype and that topical cAMP induction enhances UV resistance in Mc1r-heterozygous or -wild type individuals by increasing eumelanin deposition and by improving nucleotide excision repair. This article is protected by copyright. All rights reserved.
Bautista, R.F., Carter, K.M., Jarrett, S.G., Napier, D., Wakamatsu, K., Ito, S., and D’Orazio, J.A. Cutaneous pharmacologic cAMP induction induces melanization of the skin and improves recovery from ultraviolet injury in melanocortin 1 receptor-intact or heterozygous skin. 23707. 2019 Pigment Cell Melanoma Res.
|pathway||BSID||Nucleotide excision repair|
|pathway||BSID||Nucleotide Excision Repair|
|drug||DRUGBANK||Cyclic Adenosine Monophosphate|
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