Abstract
Ultraviolet light (UV) is an inducer of reactive oxygen species (ROS) as well as 6-4-photoproducts and cyclobutane pyrimidine dimers (CPD) in the skin, which further cause damage to the skin cells. Irradiation of cultured human melanocytes with UVB stimulated ROS production, which was reduced in cells treated with melatonin or its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5-MT). Melatonin and its derivatives also stimulated the expression of NRF2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) and its target enzymes and proteins that play an important role in cell protection from different damaging factors including UVB. Silencing of NRF2 using siRNA diminished the protective effects of melatonin, while the membrane melatonin receptors (MT1 or MT2) did not change the activities of either melatonin or its derivatives. Melatonin and its metabolites enhanced the DNA repair in melanocytes exposed to UVB and stimulated expression of p53 phosphorylated at Ser-15. In conclusion, melatonin and its metabolites protect melanocytes from UVB-induced DNA damage and oxidative stress through activation of NRF2-dependent pathways; these actions are independent of an effect on the classic membrane melatonin receptors. Thus, melatonin and its derivatives can serve as excellent protectors of melanocytes against UVB-induced pathology.
Document Type
Article
Publication Date
4-28-2017
Digital Object Identifier (DOI)
https://doi.org/10.1038/s41598-017-01305-2
Funding Information
The work was supported by NIH grant 1R01AR056666-01A2 to A.S
Related Content
Supplementary information accompanies this paper at doi: 10.1038/s41598-017-01305-2
Repository Citation
Janjetovic, Zorica; Jarrett, Stuart G.; Lee, Elizabeth F.; Duprey, Cory; Reiter, Russel J.; and Slominski, Andrzej T., "Melatonin and Its Metabolites Protect Human Melanocytes Against UVB-Induced Damage: Involvement of NRF2-Mediated Pathways" (2017). Toxicology and Cancer Biology Faculty Publications. 69.
https://uknowledge.uky.edu/toxicology_facpub/69
supplementary info
Included in
Amino Acids, Peptides, and Proteins Commons, Cell Biology Commons, Enzymes and Coenzymes Commons, Medical Toxicology Commons, Molecular Biology Commons
Notes/Citation Information
Published in Scientific Reports, v. 7, article no. 1274, p. 1-13.
© The Author(s) 2017
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