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

A.T. Slominski, Z. Janjetovic, T.K. Kim, P. Wasilewski, S. Rosas, S. Hanna, R.M. Sayre, J.C. Dowdy, W. Li, Robert Tuckey

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

© 2015 Elsevier Ltd. 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'.
Original languageEnglish
Pages (from-to)52-63
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume148
DOIs
Publication statusPublished - 2015

Fingerprint

Secosteroids
Solar radiation
Keratinocytes
Cholesterol Side-Chain Cleavage Enzyme
Radiation
Melanocytes
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Pyrimidine Dimers
Gene encoding
Oxidative stress
Comet Assay
Cholecalciferol
DNA
DNA Fragmentation
Vitamin D
DNA Damage
Assays
Oxidative Stress
Up-Regulation
Chemical activation

Cite this

Slominski, A.T. ; Janjetovic, Z. ; Kim, T.K. ; Wasilewski, P. ; Rosas, S. ; Hanna, S. ; Sayre, R.M. ; Dowdy, J.C. ; Li, W. ; Tuckey, Robert. / Novel non-calcemic secosteroids that are produced by human epidermal keratinocytes protect against solar radiation. In: Journal of Steroid Biochemistry and Molecular Biology. 2015 ; Vol. 148. pp. 52-63.
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Novel non-calcemic secosteroids that are produced by human epidermal keratinocytes protect against solar radiation. / Slominski, A.T.; Janjetovic, Z.; Kim, T.K.; Wasilewski, P.; Rosas, S.; Hanna, S.; Sayre, R.M.; Dowdy, J.C.; Li, W.; Tuckey, Robert.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 148, 2015, p. 52-63.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Novel non-calcemic secosteroids that are produced by human epidermal keratinocytes protect against solar radiation

AU - Slominski, A.T.

AU - Janjetovic, Z.

AU - Kim, T.K.

AU - Wasilewski, P.

AU - Rosas, S.

AU - Hanna, S.

AU - Sayre, R.M.

AU - Dowdy, J.C.

AU - Li, W.

AU - Tuckey, Robert

PY - 2015

Y1 - 2015

N2 - © 2015 Elsevier Ltd. 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'.

AB - © 2015 Elsevier Ltd. 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'.

U2 - 10.1016/j.jsbmb.2015.01.014

DO - 10.1016/j.jsbmb.2015.01.014

M3 - Article

VL - 148

SP - 52

EP - 63

JO - Journal of Steroid Biochemistry & Molecular Biology

JF - Journal of Steroid Biochemistry & Molecular Biology

SN - 0960-0760

ER -