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Nitric Oxide Induces Osteoblast Apoptosis through a Mitochondria-Dependent Pathway

机译:一氧化氮通过线粒体依赖性途径诱导成骨细胞凋亡

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Osteoblasts contribute to bone remodeling. Nitric oxide can regulate osteoblast activities. In this study, we attempted to evaluate the pathophysiological effects of nitric oxide on osteoblasts and its possible mechanism using neonatal rat calvarial osteoblasts as the experimental model. Exposure of osteoblasts to sodium nitroprusside, a nitric oxide donor, decreased alkaline phosphatase activities and cell viability in a concentration- and time-dependent manner. Apoptotic analysis revealed that sodium nitroprusside time-dependently increased the percentages of osteoblasts undergoing apoptosis. Administration of sodium nitroprusside reduced the mitochondrial membrane potential of osteoblasts. In parallel with the mitochondrial dysfunction, levels of intracellular reactive oxygen species and cytochrome c were significantly elevated following sodium nitroprusside administration. Exposure of osteoblasts to sodium nitroprusside significantly increased caspase-3 activity. Results of this study show that nitric oxide, decomposed from sodium nitroprusside, can induce osteoblast apoptosis through a mitochondrion-dependent cascade that causes mitochondrial dysfunction, release of intracellular reactive oxygen species and cytochrome c from mitochondria to cytoplasm, and activation of caspase-3.
机译:成骨细胞有助于骨重塑。一氧化氮可以调节成骨细胞活性。在这项研究中,我们试图评估一氧化氮对成骨细胞的病理生理学作用及其使用新生大鼠颅骨成骨细胞作为实验模型的可能机制。成骨细胞暴露于硝普钠,一氧化氮供体,以浓度和时间依赖性的方式降低碱性磷酸酶活性和细胞活力。凋亡分析显示,硝普钠依赖性增加了凋亡的成骨细胞的百分比。氮肺钠施用降低了成骨细胞的线粒体膜电位。与线粒体功能障碍平行,在硝普钠给药钠后,细胞内反应性氧物质和细胞色素C的水平显着升高。骨盆细胞暴露于硝普钠钠显着增加了Caspase-3活性。该研究的结果表明,从硝普钠分解的一氧化氮可以通过线粒体依赖性级联诱导成骨细胞凋亡,这导致线粒体功能障碍,细胞内反应性氧物质和细胞色素释放到细胞质中的细胞质,并激活Caspase-3。

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