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Photoprotective Properties of Vitamin D and Lumisterol Hydroxyderivatives

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Abstract

We have previously described new pathways of vitamin D3 activation by CYP11A1 to produce a variety of metabolites including 20(OH)D3 and 20,23(OH)2D3. These can be further hydroxylated by CYP27B1 to produce their C1α-hydroxyderivatives. CYP11A1 similarly initiates the metabolism of lumisterol (L3) through sequential hydroxylation of the side chain to produce 20(OH)L3, 22(OH)L3, 20,22(OH)2L3 and 24(OH)L3. CYP11A1 also acts on 7-dehydrocholesterol (7DHC) producing 22(OH)7DHC, 20,22(OH)27DHC and 7-dehydropregnenolone (7DHP) which can be converted to the D3 and L3 configurations following exposure to UVB. These CYP11A1-derived compounds are produced in vivo and are biologically active displaying anti-proliferative, anti-inflammatory, anti-cancer and pro-differentiation properties. Since the protective role of the classical form of vitamin D3 (1,25(OH)2D3) against UVB-induced damage is recognized, we recently tested whether novel CYP11A1-derived D3- and L3-hydroxyderivatives protect against UVB-induced damage in epidermal human keratinocytes and melanocytes. We found that along with 1,25(OH)2D3, CYP11A1-derived D3-hydroxyderivatives and L3 and its hydroxyderivatives exert photoprotective effects. These included induction of intracellular free radical scavenging and attenuation and repair of DNA damage. The protection of human keratinocytes against DNA damage included the activation of the NRF2-regulated antioxidant response, p53-phosphorylation and its translocation to the nucleus, and DNA repair induction. These data indicate that novel derivatives of vitamin D3 and lumisterol are promising photoprotective agents. However, detailed mechanisms of action, and the involvement of specific nuclear receptors, other vitamin D binding proteins or mitochondria, remain to be established.

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Acknowledgements

The study was supported by NIH grants 1R01AR073004-01A1 and R01AR071189-01A1 and by a VA merit grant (no. 1I01BX004293-01A1) to A.T.S., internal (UAB) funds to A.T.S. and C.R., by the Intramural Research Program of the NIEHS, NIH Z01-ES-101585 (to A.M.J.) and RO1 ES 026219 (to M.A.).

Author Contributions

All authors contributed to the study conception and design of the review with A.T.S. serving as the primary author.

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Authors and Affiliations

  1. Department of Dermatology, University of Alabama at Birmingham, Birmingham, Al, USA

    Andrzej T. Slominski, Zorica Janjetovic, Tae-Kang Kim, Joanna Stefan, Shariq Qayyum, Yuwei Song & Mohammad Athar

  2. Veteran Administration Medical Center, Birmingham, Al, USA

    Andrzej T. Slominski

  3. Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand

    Anyamanee Chaiprasongsuk

  4. Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Anyamanee Chaiprasongsuk & Uraiwan Panich

  5. Department of Medicine and Microbiology, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, USA

    Radomir M. Slominski, Vidya Sagar Hanumanthu & Chander Raman

  6. Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Al, USA

    Yuhua Song

  7. Department of Genetics, University of Alabama at Birmingham, Birmingham, Al, USA

    David K. Crossman

  8. Department of Medicines, Boston University, Boston, MA, USA

    Michael F. Holick

  9. Cell Biology Section, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA

    Anton M. Jetten

  10. Department of Histology, Medical University of Gdansk, Gdansk, Poland

    Michal A. Zmijewski

  11. Department of Medicine, University of Alabama at Birmingham, Birmingham, Al, USA

    Jaroslaw Zmijewski

  12. School of Molecular Sciences, The University of Western Australia, Perth, WA, Australia

    Robert C. Tuckey

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Slominski, A.T., Chaiprasongsuk, A., Janjetovic, Z. et al. Photoprotective Properties of Vitamin D and Lumisterol Hydroxyderivatives. Cell Biochem Biophys 78, 165–180 (2020). https://doi.org/10.1007/s12013-020-00913-6

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