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

Andrzej T. Slominski, Zorica Janjetovic, Tae Kang Kim, Piotr Wasilewski, Sofia Rosas, Sherie Hanna, Robert M. Sayre, John C. Dowdy, Wei Li, Robert C. Tuckey

Research output: Contribution to journalReview article

33 Citations (Scopus)

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'.

Original languageEnglish (US)
Pages (from-to)52-63
Number of pages12
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume148
DOIs
StatePublished - Jan 1 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

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

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

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 148, 01.01.2015, p. 52-63.

Research output: Contribution to journalReview article

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. / 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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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'.",
author = "Slominski, {Andrzej T.} and Zorica Janjetovic and Kim, {Tae Kang} and Piotr Wasilewski and Sofia Rosas and Sherie Hanna and Sayre, {Robert M.} and Dowdy, {John C.} and Wei Li and Tuckey, {Robert C.}",
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T1 - Novel non-calcemic secosteroids that are produced by human epidermal keratinocytes protect against solar radiation

AU - Slominski, Andrzej T.

AU - Janjetovic, Zorica

AU - Kim, Tae Kang

AU - Wasilewski, Piotr

AU - Rosas, Sofia

AU - Hanna, Sherie

AU - Sayre, Robert M.

AU - Dowdy, John C.

AU - Li, Wei

AU - Tuckey, Robert C.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 - 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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