Novel non-calcemic secosteroids that are produced by human epidermal keratinocytes protect against solar radiation. Issue 148 (April 2015)

• Record Type: Journal Article
• Authors: Slominski, Andrzej T.; Janjetovic, Zorica; Kim, Tae-Kang; Wasilewski, Piotr; Rosas, Sofia; Hanna, Sherie; Sayre, Robert M.; Dowdy, John C.; Li, Wei; Tuckey, Robert C.
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 148(2015)
• Page Start: 52
• Page End: 63
• Publication Date: 2015-04
• Subjects: Hydroxyvitamin D -- Epidermal keratinocytes -- Epidermal melanocytes -- UVB -- DNA damage -- Oxidative stress; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2015.01.014
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: We detected 20-hydroxyvitamin D3 in the human epidermis. 20-Hydroxy- and 20, 23-dihydroxyvitamin D3 attenuate oxidative stress in keratinocytes and melanocytes. 20-Hydroxy-7-dehydrocholesterol attenuates oxidative stress in keratinocytes and melanocytes. 20-Hydroxyvitamin D3 attenuates UVB induced DNA damage to a similar degree as 1, 25-dihydroxyvitamin D3. Abstract: CYP11A1 hydroxylates the side chain of vitamin D3 (D3) in a sequential fashion [D3 → 20 S (OH)D3 → 20, 23(OH)2 D3 → 17, 20, 23(OH)3 D3], in an alternative to the classical pathway of activation [D3 → 25(OH)D3 → 1, 25(OH)2 D3]. 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, H2 O2 and NO production by UVB-irradiated keratinocytes and melanocytes, with an efficacy similar to 1, 25(OH)2 D3, while 25(OH)D3 had lower efficacy. These attenuations were also seen to some extent for the 20(OH)D3 precursor, 20 S -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)2 D3. 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'.