Nitric oxide protects osteoblasts from oxidative stress-induced apoptotic insults via a mitochondria-dependent mechanism
Nitric oxide protects osteoblasts from oxidative stress-induced apoptotic insults via a mitochondria-dependent mechanism
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DOI：
10.1002/jor.20244
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发表时间：
2006-10-01
影响因子：
2.8
通讯作者：
Chen, Ruei-Ming
中科院分区：
文献类型：
--
作者：
Chang, Chia-Chen;Liao, Yi-Shyan;Chen, Ruei-Ming
一氧化氮（NO）参与成骨细胞活性的调节。本研究以新生大鼠颅骨成骨细胞为实验模型，探讨NO预处理对氧化应激诱导的成骨细胞凋亡的保护作用及其可能机制。成骨细胞暴露于0.3 mM的低浓度硝普钠（SNP）显着增加细胞NO水平，而不影响细胞活力。然而，当浓度达到2 mM的高浓度时，SNP增加细胞内活性氧的水平并诱导成骨细胞损伤。因此，在成骨细胞中施用0.3和2 mM SNP分别用作NO和氧化应激的来源。NO预处理24 h可显著改善氧化应激引起的细胞形态学改变和碱性磷酸酶活性的降低，并减少细胞死亡。氧化应激通过凋亡机制诱导成骨细胞死亡，但NO预处理保护成骨细胞免受毒性作用。线粒体膜电位显着降低暴露后的氧化应激。而NO预处理可显著降低其抑制作用。氧化应激增加细胞Bax蛋白的产生和细胞色素c从线粒体的释放。NO预处理显著降低了氧化应激引起的Bax和细胞色素c蛋白水平的增加。与细胞色素c释放平行，氧化应激诱导caspase-3活化和DNA片段化。NO预处理显著降低氧化应激增强的caspase-3活化和DNA损伤。本研究结果表明，NO预处理可以保护成骨细胞免受氧化应激诱导的凋亡损伤。这种保护作用涉及一种依赖于多巴胺的机制。(c)2006骨科研究学会。
Nitric oxide (NO) contributes to the regulation of osteoblast activities. In this study, we evaluated the protective effects of NO pretreatment on oxidative stress-induced osteoblast apoptosis and its possible mechanism using neonatal rat calvarial osteoblasts as the experimental model. Exposure of osteoblasts to sodium nitroprusside (SNP) at a low concentration of 0.3 mM significantly increased cellular NO levels without affecting cell viability. However, when the concentration reached a high concentration of 2 mM, SNP increased the levels of intracellular reactive oxygen species and induced osteoblast injuries. Thus, administration of 0.3 and 2 mM SNP in osteoblasts were respectively used as sources of NO and oxidative stress. Pretreatment with NO for 24 h significantly ameliorated the oxidative stress-caused morphological alterations and decreases in alkaline phosphatase activity, and reduced cell death. Oxidative stress induced osteoblast death via an apoptotic mechanism, but NO pretreatment protected osteoblasts against the toxic effects. The mitochondrial membrane potential was significantly reduced following exposure to the oxidative stress. However, pretreatment with NO significantly lowered the suppressive effects. Oxidative stress increased cellular Bax protein production and cytochrome c release from mitochondria. Pretreatment with NO significantly decreased oxidative stress-caused augmentation of Bax and cytochrome c protein levels. In parallel with cytochrome c release, oxidative stress induced caspase-3 activation and DNA fragmentation. Pretreatment with NO significantly reduced the oxidative stress-enhanced caspase-3 activation and DNA damage. Results of this study show that NO pretreatment can protect osteoblasts from oxidative stress-induced apoptotic insults. The protective action involves a mitochondria-dependent mechanism. (c) 2006 Orthopaedic Research Society.