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The vitamin D hormone, 1,25dihydroxyvitamin D3 (1,25(OH)2D3), and related compounds derived from vitamin D3 or lumisterol as a result of metabolism via the enzyme CYP11A1, have been shown, when applied 24 hours before or immediately after UV irradiation, to protect human skin cells and skin from DNA damage due to UV exposure, by reducing both cyclobutane pyrimidine dimers (CPD) and oxidative damage in the form of 8‐oxo‐7,8‐dihydro‐2’‐ deoxyguanosine (8‐OHdG). We now report that knockdown of either the vitamin D receptor or the endoplasmic reticulum protein ERp57 by siRNA abolished the reductions in UV‐induced DNA damage with 20‐hydroxyvitamin D3 or 24‐hydroxylumisterol3, as previously shown for 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced oxygen consumption rates in UV‐exposed and sham‐exposed human keratinocytes and reduced phosphorylation of CREB (cyclic AMP response binding element protein). Both these actions have been shown to inhibit skin carcinogenesis after chronic UV exposure, consistent with the anticarcinogenic activity of 1,25(OH)2D3. The requirement for a vitamin D receptor for the photoprotective actions of 1,25(OH)2D3 and of naturally occurring CYP11A1‐derived vitamin D related compounds may explain why mice lacking the vitamin D receptor in skin are more susceptible to UV‐induced skin cancers, whereas mice lacking the 1α‐hydroxylase and thus unable to make 1,25(OH)2D3 are not more susceptible. This article is protected by copyright. All rights reserved.
Medicine and Health Sciences
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De Silva, Warusavithana Gunawardena Manori; Han, Jeremy Zhuo Ru; Yang, Chen; Tongkao‐On, Wannit; McCarthy, Bianca Yuko; Ince, Furkan Akif; Holland, Andrew J A; Tuckey, Robert Charles; Slominski, Andrzej T; Abboud, Myriam; Dixon, Katie Marie; Rybchyn, Mark Stephen; and Mason, Rebecca Sara, "Evidence for involvement of non‐classical pathways in the protection from UV‐induced DNA damage by vitamin D‐related compounds" (2021). All Works. 4509.
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