Cited by 77Skin Protection and AgingVitamin D Research Studiesmelanin and skin pigmentation

Novel non-calcemic secosteroids that are produced by human epidermal keratinocytes protect against solar radiation

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Slominski, Andrzej T., Janjetovic, Zorica, Kim, Tae-Kang, Wasilewski, Piotr, Rosas, Sofia, Hanna, Sherie, Sayre, Robert M., Dowdy, John C. +2 more·2015·The Journal of Steroid Biochemistry and Molecular Biology

Abstract

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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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)
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
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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