Novel non-calcemic secosteroids that are produced by human epidermal keratinocytes protect against solar radiation
Open accessAbstract
CYP11A1 hydroxylates the side chain of vitamin D3 (D3) in a sequential fashion [D3→20S(OH)D3→20,23(OH)2D3→17,20,23(OH)3D3], in an alternative to the classical pathway of activation [D3→25(OH)D3→1,25(OH)2D3]. The products/intermediates of the pathway can be further modified by the action of CYP27B1. The CYP11A1-derived products are biologically active with functions determined by the lineage of the target cells. This pathway can operate in epidermal keratinocytes. To further define the role of these novel secosteroids we tested them for protective effects against UVB-induced damage in human epidermal keratinocytes, melanocytes and HaCaT keratinocytes, cultured in vitro. The secosteroids attenuated ROS, H2O2 and NO production by UVB-irradiated keratinocytes and melanocytes, with an efficacy similar to 1,25(OH)2D3, while 25(OH)D3 had lower efficacy. These attenuations were also seen to some extent for the 20(OH)D3 precursor, 20S-hydroxy-7-dehydrocholesterol. These effects were accompanied by upregulation of genes encoding enzymes responsible for defense against oxidative stress. Using immunofluorescent staining we observed that the secosteroids reduced the generation cyclobutane pyrimidine dimers in response to UVB and enhanced expression of p53 phosphorylated at Ser-15, but not at Ser-46. Additional evidence for protection against DNA damage in cells exposed to UVB and treated with secosteroids was provided by the Comet assay where DNA fragmentation was markedly reduced by 20(OH)D3 and 20,23(OH)2D3. In conclusion, novel secosteroids that can be produced by the action of CYP11A1 in epidermal keratinocytes have protective effects against UVB radiation. This article is part of a special issue entitled '17th Vitamin D Workshop'.
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Treatment with 1,25(OH)2D3 or 20(OH)D3 prior to UVB exposure protects human keratinocytes from UVB-induced damage by reducing CPD levels and stimulating expression of p53 phosphorylated at Ser-15.
“Our previous study indicated that treatment with 1,25(OH)2D3 or 20(OH)D3 prior to UVB exposure, protects human keratinocytes from UVB-induced damage by the reduction of CPD levels and stimulation of the expression of p53 phosphorylated at Ser-15 [47].”
Previous results showed a reduction in CPD damage in human keratinocytes treated with 1,25(OH)2D3 or 20(OH)D3 prior to UVB exposure.
“Our previous results showed that there was a reduction in CPD damage in human keratinocytes treated with 1,25(OH)2D3 or 20(OH)D3 prior to UVB exposure [47].”
Previous results showed stimulation of p53 phosphorylated at Ser-15 in human keratinocytes treated with 1,25(OH)2D3 or 20(OH)D3 prior to UVB exposure.
“Our previous results revealed a reduction in CPD damage, and stimulation of p53 phosphorylated at Ser-15 in human keratinocytes treated with 1,25(OH)2D3 or 20(OH)D3 prior to UVB exposure [47].”
20(OH)D3 and 20,23(OH)2D3 have ability to protect against ROS formation.
“Recent investigations have shown that like 1,25(OH)2D3, products of this pathway, 20(OH)D3 and 20,23(OH)2D3, have the ability to protect against ROS formation [47,75,76].”
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Tang, E. K. Y., Chen, J., Janjetovic, Z., Tieu, E. W., Slominski, A. T., Li, W., & Tuckey, R. C. (2013) · Drug Metabolism and Disposition · doi:10.1124/dmd.113.050955 · Cited by 42 · see citing works
Self-citationOh, D. H., Rigas, D., Cho, A., & Chan, J. Y. (2012) · FEBS Journal · doi:10.1111/febs.12005 · Cited by 37 · see citing works
(2006) · FEBS Journal · doi:10.1111/j.1742-4658.2006.05447.x · Cited by 31 · see citing works
Design, Synthesis, and Biological Action of 20R-Hydroxyvitamin D3
Lü, Y., Chen, J., Janjetović, Z., Michaels, P. D., Tang, E. K. Y., Wang, J., Tuckey, R. C., Slominski, A. T., Li, W., & Miller, D. D. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201478e · Cited by 28 · see citing works
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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Natural 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
Janjetovic, 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-citationSlominski, A. T., Kim, T.-K., Hobrath, J. V., Oak, A. S. W., Tang, E. K. Y., Tieu, E. W., Li, W., Tuckey, R. C., & Jetten, A. M. (2017) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.09.024 · Cited by 143 · see citing works
Self-citationSlominski, A. T., Brożyna, A. A., Zmijewski, M. A., Jóźwicki, W., Jetten, A. M., Mason, R. S., Tuckey, R. C., & Elmets, C. A. (2017) · Laboratory Investigation · doi:10.1038/labinvest.2017.3 · Cited by 136 · 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., Kim, T.-K., Hobrath, J. V., Janjetovic, Z., Oak, A. S. W., Postlethwaite, A., Lin, Z., Li, W., Takeda, Y., Jetten, A. M., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10202-7 · Cited by 82 · see citing works
Self-citationCooperstone, J. L., Tober, K. L., Riedl, K. M., Teegarden, M. D., Cichon, M. J., Francis, D. M., Schwartz, S. J., & Oberyszyn, T. M. (2017) · Scientific Reports · doi:10.1038/s41598-017-05568-7 · Cited by 66 · see citing works
Vitamin D derivatives enhance cytotoxic effects of H2O2 or cisplatin on human keratinocytes
Piotrowska, A., Wierzbicka, J., Ślebioda, T., Woźniak, M., Tuckey, R. C., Slominski, A. T., & Żmijewski, M. A. (2016) · Steroids · doi:10.1016/j.steroids.2016.04.002 · Cited by 48 · see citing works
Self-citation
- Authors
- Slominski, A. T., Janjetovic, Z., Kim, T.-K., Wasilewski, P., Rosas, S., Hanna, S., Sayre, R. M., Dowdy, J. C., Li, W., & Tuckey, R. C.
- Affiliations
- University of Tennessee Health Science Center (US)
- The University of Western Australia (AU)
- Corresponding author
- Slominski, Andrzej T.
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 148
- Pages
- 52-63
- ISSN
- 0960-0760 (ISSN-L)
- PMC
- PMC4369786
- OpenAlex
- W2036051073
- Cited by
- 77
- References
- 88
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 11 · 2019: 5 · 2018: 8 · 2017: 8 · 2016: 8 · 2015: 8 · 2014: 1
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UWA Profiles and Research Repository (University of Western Australia) (submittedVersion)
- Funders
- NIH (2R01AR052190-A6, AR066505-01A1, 1R01AR056666-01A2, 1R21AR063242-01A1, 1S10OD010678-01, 1S10RR026377-01)
- International Federation of Medical Student's Association (IFMSA)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- CYP11A1, UVB protection, epidermal keratinocytes, melanocytes, reactive oxygen species, nitric oxide, oxidative stress, DNA damage, cyclobutane pyrimidine dimers, p53 phosphorylation, DNA fragmentation
- MeSH terms
- Epidermal Cells, Cells, Cultured, DNA Damage, Epidermis, Humans, Hypercalcemia, Secosteroids, Ultraviolet Rays, Keratinocytes, Oxidative Stress
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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.
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