Wong G, Gupta R, Dixon K M, Deo S S, Choong S M, Halliday G M, Bishop J E, Ishizuka S, Norman A W, Posner G H, Mason R S
Department of Physiology and Institute for Biomedical Research, School of Biomedical Sciences, University of Sydney, Sydney, NSW 2006, Australia.
J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):567-70. doi: 10.1016/j.jsbmb.2004.03.072.
1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is anti-apoptotic in human keratinocytes, melanocytes and fibroblasts after ultraviolet (UV)-exposure. To date, there is no published data on the effects of 1,25(OH)(2)D(3) or its analogs on DNA damage in irradiated skin cells. In these skin cells, 24h pre-treatment with 1,25(OH)(2)D(3) dose-dependently (10(-12) to 10(-8)M) decreased CPD damage by up to 60%. This photoprotective effect was also seen if the 1,25(OH)(2)D(3) was added immediately after irradiation and was mimicked by QW-1624F2-2 (QW), a low-calcemic 1beta-hydroxymethyl-3-epi-16-ene-24,24-difluoro-26,27-bis homo hybrid analog. The well-studied low calcemic, rapid acting agonist analogs 1alpha,25(OH)(2)lumisterol(3) (JN) and 1alpha,25(OH)(2)-7-dehydrocholesterol (JM) also protected skin cells from UV-induced cell loss and CPD damage to an extent comparable with that of 1,25(OH)(2)D(3). In contrast, the rapid response antagonist analog 1beta,25(OH)(2)D(3) (HL) completely abolished the photoprotective effects (reduced cell loss and reduced CPD damage) produced by treatment with 1,25(OH)(2)D(3), JN, JM and QW. Evidence for involvement of the nitric oxide pathway in the protection from CPD damage by 1,25(OH)(2)D(3) was obtained. These data provide further evidence for a role of the vitamin D pathway in the intrinsic skin defenses against UV damage. The data also support the hypothesis that the photoprotective effects of 1,25(OH)(2)D(3) are mediated via the rapid response pathway(s).
1,25 - 二羟基维生素D(3)[1,25(OH)₂D₃]在紫外线(UV)照射后对人角质形成细胞、黑素细胞和成纤维细胞具有抗凋亡作用。迄今为止，尚无关于1,25(OH)₂D₃或其类似物对受辐照皮肤细胞DNA损伤影响的公开数据。在这些皮肤细胞中，用1,25(OH)₂D₃进行24小时预处理（剂量范围为10⁻¹²至10⁻⁸M）可使环丁烷嘧啶二聚体(CPD)损伤剂量依赖性降低高达60%。如果在照射后立即添加1,25(OH)₂D₃，也可观察到这种光保护作用，并且这种作用可被低钙血症的1β - 羟甲基 - 3 - 表 - 16 - 烯 - 24,24 - 二氟 - 26,27 - 双高杂交类似物QW - 1624F2 - 2（QW）模拟。经过充分研究的低钙血症、快速起效的激动剂类似物1α,25(OH)₂麦角钙化醇(3)(JN)和1α,25(OH)₂ - 7 - 脱氢胆固醇(JM)在一定程度上也能保护皮肤细胞免受紫外线诱导的细胞损失和CPD损伤，其程度与1,25(OH)₂D₃相当。相比之下，快速反应拮抗剂类似物1β,25(OH)₂D₃(HL)完全消除了用1,25(OH)₂D₃、JN、JM和QW处理所产生的光保护作用（减少细胞损失和减少CPD损伤）。获得了一氧化氮途径参与1,25(OH)₂D₃对CPD损伤保护作用的证据。这些数据为维生素D途径在皮肤对紫外线损伤的内在防御中的作用提供了进一步证据。这些数据也支持了1,25(OH)₂D₃的光保护作用是通过快速反应途径介导的这一假说。
