Sodium fluoride induces apoptosis in odontoblasts via a JNK-dependent mechanism
Sodium fluoride induces apoptosis in odontoblasts via a JNK-dependent mechanism
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氟化钠通过 JNK 依赖性机制诱导成牙本质细胞凋亡
DOI：
10.1016/j.tox.2013.03.016
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发表时间：
2013-06-07
期刊：
影响因子：
4.5
通讯作者：
Yu, Qing
中科院分区：
文献类型：
--
作者：
Li, Peng;Xue, Yunpeng;Yu, Qing
氟化钠(NaF)广泛用于治疗龋齿和牙本质过敏症。然而，它对成牙本质细胞的促凋亡作用可能会导致有害的副作用。本研究的目的是评价NaF对成牙本质细胞的促凋亡作用，并阐明其可能的分子机制。NaF对成牙本质细胞系细胞(OLC)产生细胞毒作用，且呈剂量和时间依赖关系。4 mM NaF作用细胞24 h后，caspase-3激活，细胞超微结构发生改变，Bax移位到线粒体，细胞色素c从线粒体膜间隙释放到胞浆中，表明氟诱导的细胞凋亡是线粒体依赖性的。氟处理还增加了JNK和ERK的磷酸化，但不增加p38的磷酸化，JNK和ERK抑制剂分别显著或部分抑制了氟诱导的成牙本质细胞凋亡。(C)2013爱思唯尔爱尔兰有限公司。保留所有权利。
Sodium fluoride (NaF) is widely used for the treatment of dental caries and dentin hypersensitivity. However, its pro-apoptotic effect on odontoblasts may lead to harmful side-effects. The purpose of this study was to evaluate the pro-apoptotic effects of NaF in odontoblasts and elucidate the possible underlying molecular mechanisms. NaF generated cytotoxic effects in odontoblast-lineage cell (OLC) in a dose- and time-dependent manner. Exposure of cells to 4 mM NaF for 24 h induced caspase-3 activation, ultrastructural alterations, and resulted in the translocation of Bax to the mitochondria and the release of cytochrome c from the mitochondrial inter-membrane space into the cytosol, indicating that fluoride-mediated apoptosis is mitochondria-dependent. Fluoride treatment also increased phosphorylation of JNK and ERK, but not p38, and apoptosis induced by fluoride was notably or partly suppressed by treatment with JNK or ERK inhibitors, respectively.Taken together, these findings suggest that NaF induces apoptosis in OLC odontoblasts through a JNK-dependent mitochondrial pathway. (C) 2013 Elsevier Ireland Ltd. All rights reserved.