Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9892057 | The Journal of Steroid Biochemistry and Molecular Biology | 2005 | 7 Pages |
Abstract
We previously reported that the natural hormone 1,25dihydroxyvitamin D3 (1,25(OH)2D3) protects human skin cells from ultraviolet radiation (UVR)-induced apoptosis. UVR-induced pre-mutagenic cyclobutane pyrimidine dimers are diminished in number from 0.5 h after cessation of UVR in all skin cell types, by treatment with three different Vitamin D compounds: by 1,25(OH)2D3, by the rapid acting, low calcemic analog, 1α,25(OH)2lumisterol3 (JN) and by the low calcemic but transcriptionally active hybrid analog 1α-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy-26,27-bis-homovitamin D3 QW-1624F2-2 (QW), which may explain the enhanced cell survival. The rapid response antagonist analog 1β,25(OH)2D3 (HL) abolished the photoprotective effects of 1,25(OH)2D3 whilst a genomic antagonist, (23S)-25-dehydro-1α-hydroxyvitamin D3-26,23-lactone (TEI-9647), had no effect. UVR increased p53 expression in human skin cells, whilst concurrent treatment with 1,25(OH)2D3 further enhanced this effect several fold, at 3 and 6 h after UVR. Combined with previously reported lower nitrite levels with 1,25(OH)2D3, this increased p53 expression may favor DNA repair over apoptosis. We now report that topical application of 1,25(OH)2D3 or QW also suppressed solar simulated UV (SSUVR-induced pyrimidine dimers in the epidermis of irradiated hairless Skh:HR1 mice, measured 24 h after irradiation. Furthermore, UVR-induced immunosuppression in the mice was markedly reduced by topical application of either 1,25(OH)2D3 or QW. These preliminary results show, for the first time, a protective effect of Vitamin D compounds against DNA photodamage in vivo.
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Authors
K.M. Dixon, S.S. Deo, G. Wong, M. Slater, A.W. Norman, J.E. Bishop, G.H. Posner, S. Ishizuka, G.M. Halliday, V.E. Reeve, R.S. Mason,