PDF(Pubmed)
Abstract：
The hormonal form of vitamin D3, 1,25(OH)2D3, reduces UV-induced DNA damage. UV exposure initiates pre-vitamin D3 production in the skin, and continued UV exposure photoisomerizes pre-vitamin D3 to produce \"over-irradiation products\" such as lumisterol3 (L3). Cytochrome P450 side-chain cleavage enzyme (CYP11A1) in skin catalyzes the conversion of L3 to produce three main derivatives: 24-hydroxy-L3 [24(OH)L3], 22-hydroxy-L3 [22(OH)L3], and 20,22-dihydroxy-L3 [20,22(OH)L3]. The current study investigated the photoprotective properties of the major over-irradiation metabolite, 24(OH)L3, in human primary keratinocytes and human skin explants. The results indicated that treatment immediately after UV with either 24(OH)L3 or 1,25(OH)2D3 reduced UV-induced cyclobutane pyrimidine dimers and oxidative DNA damage, with similar concentration response curves in keratinocytes, although in skin explants, 1,25(OH)2D3 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)L3 provided photoprotection against UV damage similar to that of 1,25(OH)2D3.
摘要：
维生素D3的激素形式，1,25（OH）2D3，减少紫外线诱导的DNA损伤。紫外线照射会引发皮肤中维生素D3的产生，和持续的紫外线曝光光异构化前维生素D3产生“过度辐射产品”，如lumisterol3（L3）。皮肤中的细胞色素P450侧链裂解酶（CYP11A1）催化L3的转化产生三种主要衍生物：24-羟基-L3[24（OH）L3]，22-羟基-L3[22(OH)L3],和20,22-二羟基-L3[20,22(OH)L3]。当前的研究调查了主要的过度辐射代谢产物的光保护特性，24（OH）L3，在人原代角质形成细胞和人皮肤外植体中。结果表明，用24（OH）L3或1,25（OH）2D3进行紫外线处理后立即减少了紫外线诱导的环丁烷嘧啶二聚体和氧化DNA损伤，在角质形成细胞中具有相似的浓度响应曲线，虽然在皮肤外植体中，1,25(OH)2D3更有效。两种化合物对DNA损伤的减少，至少在某种程度上,通过增加糖酵解增加能量可用性来增加DNA修复的结果，以及核苷酸切除修复途径中增加的DNA损伤识别蛋白。在存在较低活性氧的情况下，两种化合物都会减少紫外线诱导的DNA光致氧化。结果表明，在体外和离体条件下，24(OH)L3提供类似于1,25(OH)2D3的抗UV损伤的光保护。
