Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel-Aviv University, 6 Weizmann Street, Tel-Aviv 64239, Israel.
J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):265-7. doi: 10.1016/j.jsbmb.2010.03.047. Epub 2010 Mar 20.
Vitamin D metabolites or its less-calcemic analogs (JKF or QW) are beneficial for bone biology. We analyzed whether or not 25(OH)D3 (25), 1,25(OH)2D3 (1,25), JKF or QW regulate lipooxygenase (LO) enzymes expression and their products hydroxyeicosatetraenoic acid (12 and 15 HETE) formation as well as reactive oxygen species (ROS) production in human bone cell lines (SaOS2 and hFOB) and primary cultured human bone cells (Obs) from males or females. All compounds except 25 increased LOs mRNA expression and HETE production in female or male Obs. ROS formation was induced by JKF and QW in both cell lines, and was inhibited by different inhibitors. Baicalein (baic) an inhibitor of 12 and 15 LO activity, inhibited partially ROS formation by JKF or QW in SaSO2 and hFOB. JKF-stimulated DNA synthesis in female Obs was inhibited by baic but unchanged by addition of HETE or HETE with baic. These results indicate that vitamin D increased oxidative stress in bone cells is in part via induction of LO expression and activity. This new feature of vitamin D is probably mediated by intracellular and/or membranal receptors and its potential hazard could lead to potential damage due to increased lipid oxidation.
维生素 D 代谢物或其无钙调作用的类似物（JKF 或 QW）对骨骼生物学有益。我们分析了 25(OH)D3（25）、1,25(OH)2D3（1,25）、JKF 或 QW 是否调节脂氧合酶（LO）酶的表达及其产物羟二十碳四烯酸（12 和 15 HETE）的形成以及男性或女性来源的人骨肉瘤细胞系（SaOS2 和 hFOB）和原代培养的人成骨细胞（Obs）中的活性氧（ROS）的产生。除 25 以外的所有化合物均增加了女性或男性 Obs 中 LO 的 mRNA 表达和 HETE 的产生。JKF 和 QW 在两种细胞系中均诱导 ROS 的形成，并被不同的抑制剂抑制。12 和 15 LO 活性的抑制剂黄芩素（baic）部分抑制了 JKF 或 QW 诱导的 ROS 形成。JKF 刺激女性 Obs 中的 DNA 合成被 baic 抑制，但添加 HETE 或 HETE 与 baic 均未改变。这些结果表明，维生素 D 增加了骨细胞中的氧化应激，部分是通过诱导 LO 表达和活性来实现的。维生素 D 的这一新特征可能是通过细胞内和/或膜受体介导的，其潜在的危害可能会导致由于脂质氧化增加而导致潜在的损伤。
