Melatonin and its metabolites ameliorate ultraviolet B‐induced damage in human epidermal keratinocytes
Open accessAbstract
We investigated the protective effects of melatonin and its metabolites: 6‐hydroxymelatonin (6‐OHM), N 1‐acetyl‐N 2‐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/cm 2) 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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In human melanocytes and keratinocytes, pretreatment with melatonin decreased p53 expression, improved DNA repair, and decreased CPD generation.
“In studies of human melanocytes and keratinocytes, cells pretreated with melatonin decreased p53 expression, improved DNA repair, and decreased CPD generation [78, 79].”
From Sunscreens and Photoaging: A Review of Current Literature (2021) · cites this paper as [79]
The Results report weaker CPD staining after melatonin treatment, suggesting improved repair in human keratinocytes. But the study does not establish the claim for melanocytes, and its Results say melatonin did not significantly decrease total p53 expression; Ser-15-phosphorylated p53 increased. The CPD experiment also treated cells immediately after UVB exposure, rather than before it. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe effects of novel vitamin D3 and lumisterol derivatives, including stimulation of Nrf2-downstream genes and proteins and photoprotection, are similar to those of other synthetic and natural compounds including 1,25(OH)2D3.
“The effects of the novel vitamin D3 and lumisterol derivatives, including the stimulation of the expression of Nrf2-downstream genes and proteins, as well as the photoprotection, are similar to those described for other synthetic and natural compounds including 1,25(OH)2D3 [1,15,17,20,36,50,97].”
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Self-citationHosni-Ahmed, A., Barnes, J. D., Wan, J. Y., & Jones, T. S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0029163 · Cited by 9 · see citing works
Flagged first, then by citations
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Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism
Tan, D.-X., Manchester, L., Esteban-Zubero, E., Zhou, Z., & Reiter, R. (2015) · Molecules · doi:10.3390/molecules201018886 · Cited by 719 · see citing works
Self-citationNatural Antioxidants: Multiple Mechanisms to Protect Skin From Solar Radiation
Dunaway, S., Odin, R., Zhou, L., Ji, L., Zhang, Y., & Kadekaro, A. L. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00392 · Cited by 280 · see citing works
Sunscreens and Photoaging: A Review of Current Literature
Guan, L. L., Lim, H. W., & Mohammad, T. F. (2021) · American Journal of Clinical Dermatology · doi:10.1007/s40257-021-00632-5 · Cited by 273 · see citing works
“In studies of human melanocytes and keratinocytes, cells pretreated with melatonin decreased p53 expression, improved DNA repair, and decreased CPD generation [78, 79].”
BackgroundJanjetovic, Z., Jarrett, S. G., Lee, E. F., Duprey, C., Reiter, R. J., & Slominski, A. T. (2017) · Scientific Reports · doi:10.1038/s41598-017-01305-2 · Cited by 163 · see citing works
Self-citationChaiprasongsuk, A., Janjetovic, Z., Kim, T.-K., Jarrett, S. G., D'Orazio, J. A., Holick, M. F., Tang, E. K. Y., Tuckey, R. C., Panich, U., Li, W., et al. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101206 · Cited by 146 · see citing works
Self-citationSkobowiat, C., Brożyna, A. A., Janjetovic, Z., Jeayeng, S., Oak, A. S. W., Kim, T., Panich, U., Reiter, R. J., & Slominski, A. T. (2018) · Journal of Pineal Research · doi:10.1111/jpi.12501 · Cited by 105 · see citing works
Self-citationSlominski, A. T., Janjetovic, Z., Kim, T.-K., Wasilewski, P., Rosas, S., Hanna, S., Sayre, R. M., Dowdy, J. C., Li, W., & Tuckey, R. C. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.01.014 · Cited by 77 · see citing works
Self-citationPhenolic Melatonin-Related Compounds: Their Role as Chemical Protectors against Oxidative Stress
Galano, A., Castañeda-Arriaga, R., Pérez-González, A., Tan, D.-X., & Reiter, R. (2016) · Molecules · doi:10.3390/molecules21111442 · Cited by 60 · see citing works
Self-citationKleszczyński, K., Bilska, B., Stegemann, A., Flis, D. J., Ziolkowski, W., Pyza, E., Luger, T. A., Reiter, R. J., Böhm, M., & Slominski, A. T. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123786 · Cited by 54 · see citing works
Self-citation
- Authors
- Janjetovic, Z., Nahmias, Z. P., Hanna, S., Jarrett, S. G., Kim, T., Reiter, R. J., & Slominski, A. T.
- Affiliations
- Department of Pathology and Laboratory Medicine Cancer Research Building Memphis TN USA
- University of Kentucky (US)
- The University of Texas at San Antonio Health Science Center (US)
- Venue
- Journal of Pineal Research
- Publisher
- Wiley
- Published
- 2014-06-28
- Volume
- 57
- Issue
- 1
- Pages
- 90-102
- ISSN
- 0742-3098 (ISSN-L)
- 1600-079X
- PMC
- PMC4106994
- OpenAlex
- W2093516261
- Cited by
- 113
- References
- 84
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 12 · 2023: 6 · 2022: 11 · 2021: 11 · 2020: 11 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 8 · 2015: 9 · 2014: 3
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Pineal Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (1R01AR056666-01A2)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- melatonin, melatonin metabolites, UV-B radiation, human keratinocytes, photoprotection, reactive oxygen species, oxidative stress, DNA repair, cyclobutane pyrimidine dimers, glutathione, N-acetylserotonin, 6-hydroxymelatonin, AFMK, 5-methoxytryptamine, p53 phosphorylation, cell viability
- MeSH terms
- Cell Line, DNA Damage, Humans, Kynuramine, Melatonin, Serotonin, Ultraviolet Rays, Keratinocytes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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