CYP11A1 in skin: An alternative route to photoprotection by vitamin D compounds

W. Tongkao-On, S.E. Carter, V.E. Reeve, K.M. Dixon, C. Gordon-Thomson, G.M. Halliday, Robert Tuckey, R.S. Mason

Research output: Contribution to journalArticle

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Abstract

© 2014 Published by Elsevier Ltd. All rights reserved. Topical 1,25-dihydroxyvitamin D (1,25D) and other vitamin D compounds have been shown to protect skin from damage by ultraviolet radiation (UVR) in a process that requires the vitamin D receptor. Yet, while mice which do not express the vitamin D receptor are more susceptible to photocarcinogenesis, mice unable to 1α-hydroxylate 25-hydroxyvitamin D to form 1,25D do not show increased susceptibility to UVR-induced skin tumors. A possible explanation is that an alternative pathway, which does not involve 1α-hydroxylation, may produce photoprotective compounds from vitamin D. The cholesterol side chain cleavage enzyme CYP11A1 is expressed in skin and produces 20-hydroxyvitamin D3 (20OHD) as a major product of vitamin D3. We examined whether topical 20OHD would affect UVR-induced DNA damage, inflammatory edema or immune suppression produced in Skh:hr1 mice. Photoprotection by 20OHD at 23 or 46 pmol/cm2 against cyclobutane pyrimidine dimers (DNA lesions) after UVR in mice was highly effective, up to 98 ± 0.8%, (p <0.001) and comparable to that of 1,25D. Sunburn edema measured as skinfold thickness 24 h after UVR was also significantly reduced by 20OHD (p <0.001). In studies of contact hypersensitivity (CHS), which is suppressed by UVR, topical application of 20OHD to mice protected against UVR-induced immunosuppression (p <0.05), similar to the effect of 1,25D at similar doses (46 ± 0.6% protection with 20OHD, 44 ± 0.5% with 1,25D). Both UVR-induced DNA damage and immunosuppression contribute to increased susceptibility to UVR-induced skin tumors. This study indicates a potentially anti-photocarcinogenic role of the naturally occurring vitamin D metabolite, 20OHD, which does not depend on 1α-hydroxylation for generation. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.
Original languageEnglish
Pages (from-to)72-78
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume148
DOIs
Publication statusPublished - Apr 2015

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Cholesterol Side-Chain Cleavage Enzyme
Vitamin D
Ultraviolet radiation
Skin
Radiation
Hydroxylation
Calcitriol Receptors
Immunosuppression
DNA Damage
Tumors
DNA
Edema
Sunburn
Pyrimidine Dimers
Skinfold Thickness
Cholecalciferol
Contact Dermatitis
Metabolites
Neoplasms
1,25-dihydroxyvitamin D

Cite this

Tongkao-On, W., Carter, S. E., Reeve, V. E., Dixon, K. M., Gordon-Thomson, C., Halliday, G. M., ... Mason, R. S. (2015). CYP11A1 in skin: An alternative route to photoprotection by vitamin D compounds. Journal of Steroid Biochemistry and Molecular Biology, 148, 72-78. https://doi.org/10.1016/j.jsbmb.2014.11.015
Tongkao-On, W. ; Carter, S.E. ; Reeve, V.E. ; Dixon, K.M. ; Gordon-Thomson, C. ; Halliday, G.M. ; Tuckey, Robert ; Mason, R.S. / CYP11A1 in skin: An alternative route to photoprotection by vitamin D compounds. In: Journal of Steroid Biochemistry and Molecular Biology. 2015 ; Vol. 148. pp. 72-78.
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abstract = "{\circledC} 2014 Published by Elsevier Ltd. All rights reserved. Topical 1,25-dihydroxyvitamin D (1,25D) and other vitamin D compounds have been shown to protect skin from damage by ultraviolet radiation (UVR) in a process that requires the vitamin D receptor. Yet, while mice which do not express the vitamin D receptor are more susceptible to photocarcinogenesis, mice unable to 1α-hydroxylate 25-hydroxyvitamin D to form 1,25D do not show increased susceptibility to UVR-induced skin tumors. A possible explanation is that an alternative pathway, which does not involve 1α-hydroxylation, may produce photoprotective compounds from vitamin D. The cholesterol side chain cleavage enzyme CYP11A1 is expressed in skin and produces 20-hydroxyvitamin D3 (20OHD) as a major product of vitamin D3. We examined whether topical 20OHD would affect UVR-induced DNA damage, inflammatory edema or immune suppression produced in Skh:hr1 mice. Photoprotection by 20OHD at 23 or 46 pmol/cm2 against cyclobutane pyrimidine dimers (DNA lesions) after UVR in mice was highly effective, up to 98 ± 0.8{\%}, (p <0.001) and comparable to that of 1,25D. Sunburn edema measured as skinfold thickness 24 h after UVR was also significantly reduced by 20OHD (p <0.001). In studies of contact hypersensitivity (CHS), which is suppressed by UVR, topical application of 20OHD to mice protected against UVR-induced immunosuppression (p <0.05), similar to the effect of 1,25D at similar doses (46 ± 0.6{\%} protection with 20OHD, 44 ± 0.5{\%} with 1,25D). Both UVR-induced DNA damage and immunosuppression contribute to increased susceptibility to UVR-induced skin tumors. This study indicates a potentially anti-photocarcinogenic role of the naturally occurring vitamin D metabolite, 20OHD, which does not depend on 1α-hydroxylation for generation. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.",
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Tongkao-On, W, Carter, SE, Reeve, VE, Dixon, KM, Gordon-Thomson, C, Halliday, GM, Tuckey, R & Mason, RS 2015, 'CYP11A1 in skin: An alternative route to photoprotection by vitamin D compounds' Journal of Steroid Biochemistry and Molecular Biology, vol. 148, pp. 72-78. https://doi.org/10.1016/j.jsbmb.2014.11.015

CYP11A1 in skin: An alternative route to photoprotection by vitamin D compounds. / Tongkao-On, W.; Carter, S.E.; Reeve, V.E.; Dixon, K.M.; Gordon-Thomson, C.; Halliday, G.M.; Tuckey, Robert; Mason, R.S.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 148, 04.2015, p. 72-78.

Research output: Contribution to journalArticle

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AU - Tongkao-On, W.

AU - Carter, S.E.

AU - Reeve, V.E.

AU - Dixon, K.M.

AU - Gordon-Thomson, C.

AU - Halliday, G.M.

AU - Tuckey, Robert

AU - Mason, R.S.

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N2 - © 2014 Published by Elsevier Ltd. All rights reserved. Topical 1,25-dihydroxyvitamin D (1,25D) and other vitamin D compounds have been shown to protect skin from damage by ultraviolet radiation (UVR) in a process that requires the vitamin D receptor. Yet, while mice which do not express the vitamin D receptor are more susceptible to photocarcinogenesis, mice unable to 1α-hydroxylate 25-hydroxyvitamin D to form 1,25D do not show increased susceptibility to UVR-induced skin tumors. A possible explanation is that an alternative pathway, which does not involve 1α-hydroxylation, may produce photoprotective compounds from vitamin D. The cholesterol side chain cleavage enzyme CYP11A1 is expressed in skin and produces 20-hydroxyvitamin D3 (20OHD) as a major product of vitamin D3. We examined whether topical 20OHD would affect UVR-induced DNA damage, inflammatory edema or immune suppression produced in Skh:hr1 mice. Photoprotection by 20OHD at 23 or 46 pmol/cm2 against cyclobutane pyrimidine dimers (DNA lesions) after UVR in mice was highly effective, up to 98 ± 0.8%, (p <0.001) and comparable to that of 1,25D. Sunburn edema measured as skinfold thickness 24 h after UVR was also significantly reduced by 20OHD (p <0.001). In studies of contact hypersensitivity (CHS), which is suppressed by UVR, topical application of 20OHD to mice protected against UVR-induced immunosuppression (p <0.05), similar to the effect of 1,25D at similar doses (46 ± 0.6% protection with 20OHD, 44 ± 0.5% with 1,25D). Both UVR-induced DNA damage and immunosuppression contribute to increased susceptibility to UVR-induced skin tumors. This study indicates a potentially anti-photocarcinogenic role of the naturally occurring vitamin D metabolite, 20OHD, which does not depend on 1α-hydroxylation for generation. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

AB - © 2014 Published by Elsevier Ltd. All rights reserved. Topical 1,25-dihydroxyvitamin D (1,25D) and other vitamin D compounds have been shown to protect skin from damage by ultraviolet radiation (UVR) in a process that requires the vitamin D receptor. Yet, while mice which do not express the vitamin D receptor are more susceptible to photocarcinogenesis, mice unable to 1α-hydroxylate 25-hydroxyvitamin D to form 1,25D do not show increased susceptibility to UVR-induced skin tumors. A possible explanation is that an alternative pathway, which does not involve 1α-hydroxylation, may produce photoprotective compounds from vitamin D. The cholesterol side chain cleavage enzyme CYP11A1 is expressed in skin and produces 20-hydroxyvitamin D3 (20OHD) as a major product of vitamin D3. We examined whether topical 20OHD would affect UVR-induced DNA damage, inflammatory edema or immune suppression produced in Skh:hr1 mice. Photoprotection by 20OHD at 23 or 46 pmol/cm2 against cyclobutane pyrimidine dimers (DNA lesions) after UVR in mice was highly effective, up to 98 ± 0.8%, (p <0.001) and comparable to that of 1,25D. Sunburn edema measured as skinfold thickness 24 h after UVR was also significantly reduced by 20OHD (p <0.001). In studies of contact hypersensitivity (CHS), which is suppressed by UVR, topical application of 20OHD to mice protected against UVR-induced immunosuppression (p <0.05), similar to the effect of 1,25D at similar doses (46 ± 0.6% protection with 20OHD, 44 ± 0.5% with 1,25D). Both UVR-induced DNA damage and immunosuppression contribute to increased susceptibility to UVR-induced skin tumors. This study indicates a potentially anti-photocarcinogenic role of the naturally occurring vitamin D metabolite, 20OHD, which does not depend on 1α-hydroxylation for generation. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

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