Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways

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 reduc...

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Autores principales:	Zorica Janjetovic, Stuart G. Jarrett, Elizabeth F. Lee, Cory Duprey, Russel J. Reiter, Andrzej T. Slominski
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4ecbb7899b874c869da790e441ecfd5d
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spelling	oai:doaj.org-article:4ecbb7899b874c869da790e441ecfd5d2021-12-02T16:06:53ZMelatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways10.1038/s41598-017-01305-22045-2322https://doaj.org/article/4ecbb7899b874c869da790e441ecfd5d2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01305-2https://doaj.org/toc/2045-2322Abstract 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.Zorica JanjetovicStuart G. JarrettElizabeth F. LeeCory DupreyRussel J. ReiterAndrzej T. SlominskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zorica Janjetovic Stuart G. Jarrett Elizabeth F. Lee Cory Duprey Russel J. Reiter Andrzej T. Slominski Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways
description	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.
format	article
author	Zorica Janjetovic Stuart G. Jarrett Elizabeth F. Lee Cory Duprey Russel J. Reiter Andrzej T. Slominski
author_facet	Zorica Janjetovic Stuart G. Jarrett Elizabeth F. Lee Cory Duprey Russel J. Reiter Andrzej T. Slominski
author_sort	Zorica Janjetovic
title	Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways
title_short	Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways
title_full	Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways
title_fullStr	Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways
title_full_unstemmed	Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways
title_sort	melatonin and its metabolites protect human melanocytes against uvb-induced damage: involvement of nrf2-mediated pathways
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4ecbb7899b874c869da790e441ecfd5d
work_keys_str_mv	AT zoricajanjetovic melatoninanditsmetabolitesprotecthumanmelanocytesagainstuvbinduceddamageinvolvementofnrf2mediatedpathways AT stuartgjarrett melatoninanditsmetabolitesprotecthumanmelanocytesagainstuvbinduceddamageinvolvementofnrf2mediatedpathways AT elizabethflee melatoninanditsmetabolitesprotecthumanmelanocytesagainstuvbinduceddamageinvolvementofnrf2mediatedpathways AT coryduprey melatoninanditsmetabolitesprotecthumanmelanocytesagainstuvbinduceddamageinvolvementofnrf2mediatedpathways AT russeljreiter melatoninanditsmetabolitesprotecthumanmelanocytesagainstuvbinduceddamageinvolvementofnrf2mediatedpathways AT andrzejtslominski melatoninanditsmetabolitesprotecthumanmelanocytesagainstuvbinduceddamageinvolvementofnrf2mediatedpathways
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Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways

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