Institute of Endocrinology, Metabolism and Hypertension Tel-Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel.
J Steroid Biochem Mol Biol. 2011 Jan;123(1-2):85-9. doi: 10.1016/j.jsbmb.2010.11.010. Epub 2010 Nov 24.
Vitamin D metabolites and its less-calcemic analogs (vitamin D compounds) are beneficial for bone and modulate cell growth and energy metabolism. We now analyze whether 25(OH)D(3) (25D), 1,25(OH)(2)D(3) (1,25D), 24,25(OH)(2)D(3) (24,25D), JKF1624F(2)-2 (JKF) or QW1624F(2)-2 (QW) regulate lipooxygenase (LO) mRNA expression and its products; hydroxyl-eicosatetraenoic acid (12 and 15HETE) formation, as well as reactive oxygen species (ROS) production in human bone cell line (SaOS2) and their interplay with modulation of cell proliferation and energy metabolism. All compounds except 25D increased 12LO mRNA expression and modulated 12 and 15HETE production whereas ROS production was increased by all compounds, and inhibited by NADPH oxidase inhibitors diphenyleneiodonium (DPI) and N-acetylcysteine (NAc). Baicaleine (baic) the inhibitor of 12 and 15LO activity blocked only slightly the stimulation of DNA synthesis by all compounds, whereas DPI inhibited almost completely the stimulation of DNA and CK by all compounds. Treatments of cells with 12 or 15HETE increased DNA synthesis and CK that were only slightly inhibited by DPI. These results indicate that vitamin D compounds increased oxidative stress in osteoblasts in part via induction of LO expression and activity. The increased ROS production mediates partially elevated cell proliferation and energy metabolism, whereas the LO mediation is not essential. This new feature of vitamin D compounds is mediated by intracellular and/or membranal binding sites and its potential hazard could lead to damage due to increased lipid oxidation, although the transient mediation of ROS in cell proliferation is beneficial to bone growth in a yet unknown mechanism.
维生素 D 代谢物及其无钙调活性类似物（维生素 D 化合物）对骨骼有益，能调节细胞生长和能量代谢。我们现在分析 25（OH）D（3）（25D）、1,25（OH）（2）D（3）（1,25D）、24,25（OH）（2）D（3）（24,25D）、JKF1624F（2）-2（JKF）或 QW1624F（2）-2（QW）是否调节人骨肉瘤细胞系（SaOS2）中的脂加氧酶（LO）mRNA 表达及其产物；羟基二十碳四烯酸（12 和 15HETE）形成以及活性氧（ROS）产生，以及它们与细胞增殖和能量代谢调节的相互作用。除 25D 外，所有化合物均增加 12LO mRNA 表达并调节 12 和 15HETE 产生，而所有化合物均增加 ROS 产生，并被 NADPH 氧化酶抑制剂二苯并碘（DPI）和 N-乙酰半胱氨酸（NAc）抑制。12 和 15LO 活性抑制剂白杨素（baic）仅轻微抑制所有化合物刺激的 DNA 合成，而 DPI 几乎完全抑制所有化合物刺激的 DNA 和 CK。用 12 或 15HETE 处理细胞可增加 DNA 合成和 CK，而 DPI 仅轻微抑制其增加。这些结果表明，维生素 D 化合物通过诱导 LO 表达和活性，部分增加成骨细胞中的氧化应激。增加的 ROS 产生部分介导升高的细胞增殖和能量代谢，而 LO 介导并非必需。维生素 D 化合物的这一新特征是通过细胞内和/或膜结合位点介导的，其潜在危害可能导致由于脂质氧化增加而导致的损伤，尽管 ROS 在细胞增殖中的短暂介导对于骨骼生长是有益的，但机制尚不清楚。
