The Over-Irradiation Metabolite Derivative, 24-Hydroxylumister-ol3, Reduces UV-Induced Damage in Skin

The hormonal form of vitamin D-3, 1,25(OH)(2)D-3, reduces UV-induced DNA damage. UV exposure initiates pre-vitamin D-3 production in the skin, and continued UV exposure photoisomerizes pre-vitamin D-3 to produce "over-irradiation products" such as lumisterol(3) (L-3). Cytochrome P450 side-chain cleavage enzyme (CYP11A1) in skin catalyzes the conversion of L-3 to produce three main derivatives: 24-hydroxy-L-3 [24(OH)L-3], 22-hydroxy-L-3 [22(OH)L-3], and 20,22-dihydroxy-L-3 [20,22(OH)L-3]. The current study investigated the photoprotective properties of the major over-irradiation metabolite, 24(OH)L-3, in human primary keratinocytes and human skin explants. The results indicated that treatment immediately after UV with either 24(OH)L-3 or 1,25(OH)(2)D-3 reduced UV-induced cyclobutane pyrimidine dimers and oxidative DNA damage, with similar concentration response curves in keratinocytes, although in skin explants, 1,25(OH)(2)D-3 was more potent. The reductions in DNA damage by both compounds were, at least in part, the result of increased DNA repair through increased energy availability via increased glycolysis, as well as increased DNA damage recognition proteins in the nucleotide excision repair pathway. Reductions in UV-induced DNA photolesions by either compound occurred in the presence of lower reactive oxygen species. The results indicated that under in vitro and ex vivo conditions, 24(OH)L-3 provided photoprotection against UV damage similar to that of 1,25(OH)(2)D-3.