Cutaneous pharmacologic cAMP induction induces melanization of the skin and improves recovery from ultraviolet injury in melanocortin 1 receptor-intact or heterozygous skin.

Cutaneous pharmacologic cAMP induction induces melanization of the skin and improves recovery from ultraviolet injury in melanocortin 1 receptor-intact or heterozygous skin.

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.

Concepts Keywords
Allele Radiation
CAMP Epidermis
DNA Amelanism
Epidermal Melanocortin receptor
Eumelanin Melanocyte
Heterozygosity Melanin
Heterozygous Melanoma
Homozygous G protein-coupled receptors
Inflammation Melanocortin 1 receptor
Mc1r Skin pigmentation
MC1R Hair color
Melanin Branches of biology
Melanization Radiation
Melanized Recovery ultraviolet injury
Melanocytes UV mediated inflammation
Melanoma Melanoma
Nucleotide Excision Repair
Pharmacologic
Phenotype
Pigment
Topical
Ultraviolet
UV

Semantics

Type Source Name
pathway BSID Nucleotide excision repair
pathway BSID Nucleotide Excision Repair
disease MESH inflammation
drug DRUGBANK Colforsin
pathway BSID DNA Repair
gene UNIPROT KITLG
gene UNIPROT KRT14
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT MC1R
gene UNIPROT CHAMP1
gene UNIPROT CAMP
drug DRUGBANK Cyclic Adenosine Monophosphate

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