We have previously described new pathways of vitamin D3 activation by CYP11A1 to produce a variety of metabolites including 20(OH)D3 and 20,23(OH)₂D3. These can be further hydroxylated by CYP27B1 to produce their C1α-hydroxyderivatives. CYP11A1 similarly initiates the metabolism of lumisterol (L3) through sequential hydroxylation of the side chain to produce 20(OH)L3, 22(OH)L3, 20,22(OH)₂L3 and 24(OH)L3. CYP11A1 also acts on 7-dehydrocholesterol (7DHC) producing 22(OH)7DHC, 20,22(OH)₂7DHC and 7-dehydropregnenolone (7DHP) which can be converted to the D3 and L3 configurations following exposure to UVB. These CYP11A1-derived compounds are produced in vivo and are biologically active displaying anti-proliferative, anti-inflammatory, anti-cancer and pro-differentiation properties. Since the protective role of the classical form of vitamin D3 (1,25(OH)₂D3) against UVB-induced damage is recognized, we recently tested whether novel CYP11A1-derived D3- and L3-hydroxyderivatives protect against UVB-induced damage in epidermal human keratinocytes and melanocytes. We found that along with 1,25(OH)₂D3, CYP11A1-derived D3-hydroxyderivatives and L3 and its hydroxyderivatives exert photoprotective effects. These included induction of intracellular free radical scavenging and attenuation and repair of DNA damage. The protection of human keratinocytes against DNA damage included the activation of the NRF2-regulated antioxidant response, p53-phosphorylation and its translocation to the nucleus, and DNA repair induction. These data indicate that novel derivatives of vitamin D3 and lumisterol are promising photoprotective agents. However, detailed mechanisms of action, and the involvement of specific nuclear receptors, other vitamin D binding proteins or mitochondria, remain to be established.

中文翻译：

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维生素 D 和光甾醇羟基衍生物的光保护特性。

我们之前已经描述了 CYP11A1 激活维生素 D3 以产生多种代谢物的新途径，包括 20(OH)D3 和 20,23(OH) ₂ D3。这些可以被 CYP27B1 进一步羟基化以产生它们的 C1α-羟基衍生物。CYP11A1 类似地通过侧链的连续羟基化启动光甾醇 (L3) 的代谢，产生 20(OH)L3、22(OH)L3、20,22(OH) 2 L3 和 24(OH) _L3。CYP11A1 还作用于 7-脱氢胆固醇 (7DHC)，产生 22(OH)7DHC、20,22(OH) ₂7DHC 和 7-脱氢孕烯醇酮 (7DHP)，在暴露于 UVB 后可转化为 D3 和 L3 配置。这些 CYP11A1 衍生化合物在体内产生，具有生物活性，具有抗增殖、抗炎、抗癌和促分化等特性。由于经典形式的维生素 D3 (1,25(OH) ₂ D3) 对 UVB 引起的损伤的保护作用已得到认可，我们最近测试了新型 CYP11A1 衍生的 D3- 和 L3-羟基衍生物是否可以防止 UVB 引起的损伤表皮人类角质形成细胞和黑色素细胞。我们发现连同 1,25(OH) ₂D3、CYP11A1 衍生的 D3-羟基衍生物和 L3 及其羟基衍生物发挥光保护作用。这些包括诱导细胞内自由基清除以及 DNA 损伤的减弱和修复。保护人角质形成细胞免受 DNA 损伤包括激活 NRF2 调节的抗氧化反应、p53 磷酸化及其向细胞核的易位以及 DNA 修复诱导。这些数据表明，维生素 D3 和光甾醇的新型衍生物是很有前途的光保护剂。然而，详细的作用机制以及特定核受体、其他维生素 D 结合蛋白或线粒体的参与仍有待确定。