Melatonin and its metabolites ameliorate ultraviolet B-induced damage in human epidermal keratinocytes

Zorica Janjetovic, Zachary P. Nahmias, Sherie Hanna, Stuart G. Jarrett, Tae Kang Kim, Russel J Reiter, Adrzej T. Slominski

Research output: Contribution to journalArticle

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Abstract

We investigated the protective effects of melatonin and its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5-MT) in human keratinocytes against a range of doses (25, 50, and 75 mJ/cm2) of ultraviolet B (UVB) radiation. There was significant reduction in the generation of reactive oxygen species (50-60%) when UVB-exposed keratinocytes were treated with melatonin or its derivatives. Similarly, melatonin and its metabolites reduced the nitrite and hydrogen peroxide levels that were induced by UVB as early as 30 min after the exposure. Moreover, melatonin and its metabolites enhanced levels of reduced glutathione in keratinocytes within 1 hr after UVB exposure in comparison with control cells. Using proliferation assay, we observed a dose-dependent increase in viability of UVB-irradiated keratinocytes that were treated with melatonin or its derivatives after 48 hr. Using the dot-blot technique and immunofluorescent staining we also observed that melatonin and its metabolites enhanced the DNA repair capacity of UVB-induced pyrimidine photoproducts (6-4)or cyclobutane pyrimidine dimers generation in human keratinocytes. Additional evidence for induction of DNA repair in cells exposed to UVB and treated with the indole compounds was shown using the Comet assay. Finally, melatonin and its metabolites further enhanced expression of p53 phosphorylated at Ser-15 but not at Ser-46 or its nonphosphorylated form. In conclusion, melatonin, its precursor NAS, and its metabolites 6-OHM, AFMK, 5-MT, which are endogenously produced in keratinocytes, protect these cells against UVB-induced oxidative stress and DNA damage.

Original languageEnglish (US)
Pages (from-to)90-102
Number of pages13
JournalJournal of Pineal Research
Volume57
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Melatonin
Keratinocytes
5-Methoxytryptamine
DNA Repair
Pyrimidine Dimers
Comet Assay
Nitrites
Hydrogen Peroxide
DNA Damage
Glutathione
Reactive Oxygen Species
Oxidative Stress
Radiation
Staining and Labeling

Keywords

  • 5-methoxytryptamine
  • 6-hydroxymelatonin
  • DNA damage
  • epidermal keratinocytes
  • melatonin
  • N-acetylserotonin
  • N1-acetyl-N2-formyl-5- methoxykynuramine
  • ultraviolet B

ASJC Scopus subject areas

  • Endocrinology
  • Medicine(all)

Cite this

Melatonin and its metabolites ameliorate ultraviolet B-induced damage in human epidermal keratinocytes. / Janjetovic, Zorica; Nahmias, Zachary P.; Hanna, Sherie; Jarrett, Stuart G.; Kim, Tae Kang; Reiter, Russel J; Slominski, Adrzej T.

In: Journal of Pineal Research, Vol. 57, No. 1, 2014, p. 90-102.

Research output: Contribution to journalArticle

Janjetovic, Zorica ; Nahmias, Zachary P. ; Hanna, Sherie ; Jarrett, Stuart G. ; Kim, Tae Kang ; Reiter, Russel J ; Slominski, Adrzej T. / Melatonin and its metabolites ameliorate ultraviolet B-induced damage in human epidermal keratinocytes. In: Journal of Pineal Research. 2014 ; Vol. 57, No. 1. pp. 90-102.
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AU - Kim, Tae Kang

AU - Reiter, Russel J

AU - Slominski, Adrzej T.

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AB - We investigated the protective effects of melatonin and its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5-MT) in human keratinocytes against a range of doses (25, 50, and 75 mJ/cm2) of ultraviolet B (UVB) radiation. There was significant reduction in the generation of reactive oxygen species (50-60%) when UVB-exposed keratinocytes were treated with melatonin or its derivatives. Similarly, melatonin and its metabolites reduced the nitrite and hydrogen peroxide levels that were induced by UVB as early as 30 min after the exposure. Moreover, melatonin and its metabolites enhanced levels of reduced glutathione in keratinocytes within 1 hr after UVB exposure in comparison with control cells. Using proliferation assay, we observed a dose-dependent increase in viability of UVB-irradiated keratinocytes that were treated with melatonin or its derivatives after 48 hr. Using the dot-blot technique and immunofluorescent staining we also observed that melatonin and its metabolites enhanced the DNA repair capacity of UVB-induced pyrimidine photoproducts (6-4)or cyclobutane pyrimidine dimers generation in human keratinocytes. Additional evidence for induction of DNA repair in cells exposed to UVB and treated with the indole compounds was shown using the Comet assay. Finally, melatonin and its metabolites further enhanced expression of p53 phosphorylated at Ser-15 but not at Ser-46 or its nonphosphorylated form. In conclusion, melatonin, its precursor NAS, and its metabolites 6-OHM, AFMK, 5-MT, which are endogenously produced in keratinocytes, protect these cells against UVB-induced oxidative stress and DNA damage.

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