In vivo relevance for photoprotection by the vitamin D rapid response pathway
In vivo relevance for photoprotection by the vitamin D rapid response pathway
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DOI：
10.1016/j.jsbmb.2006.11.016
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发表时间：
2007-03-01
影响因子：
4.1
通讯作者：
Mason, R. S.
中科院分区：
文献类型：
--
作者：
Dixon, K. M.;Deo, S. S.;Mason, R. S.
维生素 D 是通过皮肤中的 7-脱氢胆固醇暴露于紫外线照射 (UVR) 产生的，并在皮肤中进一步转化为生物活性代谢物 1,25-二羟基维生素 D-3 (1,25(OH)(2)D-3) 和其他化合物。 UVR 还会导致 DNA 损伤，产生环丁烷嘧啶二聚体 (CPD)。我们之前报道过皮摩尔浓度的 1,25(OH)(2)D-3 可以保护人类皮肤细胞免受 UVR 诱导的细胞凋亡，并减少存活细胞的 CPD。 1,25(OH)(2)D-3 已被证明可通过两种途径产生生物反应 - 经典的类固醇受体/基因组途径或由假定的膜受体介导的快速非基因组途径。快速反应途径是否具有生理相关性尚不清楚。一种顺式锁定、速效激动剂 1,25(OH)(2)lumisterol(3) (JN)，完全模仿 1,25(OH)(2)D-3 的作用，可减少 UVR 后成纤维细胞和角质形成细胞的损失以及 CPD 损伤。 1,25(OH)(2)D-3 的作用可以被速效拮抗剂消除，但不能被基因组拮抗剂消除。 Skh:hr1 小鼠暴露于三倍最小红细胞剂量的太阳模拟 UVR 并在 UVR 后立即局部用 1,25(OH)(2)D-3 或 JN 治疗，结果显示 UVR 诱导的 UVR 诱导的晒伤细胞（分别为 p < 0.01 和 < 0.05）、CPD（两者均 p < 0.01）和免疫抑制（两者 P < 0.001）减少。媒介物处理的小鼠。这些结果首次显示了由维生素 D 系统的速效类似物介导的体内生物反应。这些数据支持了 1,25(OH)(2)D-3 通过快速途径发挥其光保护作用的假设，并提出了皮肤中产生的其他 D 化合物可能有助于光保护作用的可能性。
Vitamin D is produced by exposure of 7-dehydrocholesterol in the skin to UV irradiation (UVR) and further converted in the skin to the biologically active metabolite, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) and other compounds. UVR also results in DNA damage producing cyclobutane pyrimidine dimers (CPD). We previously reported that 1,25(OH)(2)D-3 at picomolar concentrations, protects human skin cells from UVR-induced apoptosis, and decreases CPD in surviving cells. 1,25(OH)(2)D-3 has been shown to generate biological responses via two pathways-the classical steroid receptor/genomic pathway or a rapid, non-genomic pathway mediated by a putative membrane receptor. Whether the rapid response pathway is physiologically relevant is unclear. A cis-locked, rapid-acting agonist 1,25(OH)(2)lumisterol(3) (JN), entirely mimicked the actions of 1,25(OH)(2)D-3 to reduce fibroblast and keratinocyte loss and CPD damage after UVR. The effects of 1,25(OH)(2)D-3 were abolished by a rapid-acting antagonist, but not by a genomic antagonist. Skh:hr1 mice exposed to three times the minimal erythernal dose of solar-simulated UVR and treated topically with 1,25(OH)(2)D-3 or JN immediately after UVR showed reduction in UVR-induced UVR-induced sunburn cells (p < 0.01 and < 0.05, respectively), CPD (p < 0.01 for both) and immunosuppression (P < 0.001 for both) compared with vehicle-treated mice. These results show for the first time an in vivo biological response mediated by a rapid-acting analog of the vitamin D system. The data support the hypothesis that 1,25(OH)(2)D-3 exerts its photoprotective effects via the rapid pathway and raise the possibility that other D compounds produced in skin may contribute to the photoprotective effects.