The vicious circle between mitochondrial oxidative stress and dynamic abnormality mediates triethylene glycol dimethacrylate-induced preodontoblast apoptosis
The vicious circle between mitochondrial oxidative stress and dynamic abnormality mediates triethylene glycol dimethacrylate-induced preodontoblast apoptosis
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DOI：
10.1016/j.freeradbiomed.2019.02.013
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发表时间：
2019-04-01
影响因子：
7.4
通讯作者：
Pan, Y. H.
中科院分区：
文献类型：
--
作者：
Huang, S. B.;Jin, X.;Pan, Y. H.
氧化应激（OS）在三甘醇二甲基丙烯酸酯（TEGDMA，牙科树脂的主要成分）诱导的牙髓细胞凋亡中起着至关重要的作用。线粒体是调节OS平衡的重要靶细胞器，同时，与线粒体功能障碍相关的线粒体动力学失衡是氧化损伤的主要分子机制之一。然而，这些线粒体依赖性途径是否参与了 TDGDMA 诱导的牙髓细胞凋亡仍不清楚。我们证明，TEGDMA 以时间和剂量依赖性方式降低小鼠前成牙本质细胞（mDPC6T 细胞系）的活力并诱导细胞凋亡。此外，TEGDMA 提高了线粒体 OS 状态并诱导线粒体功能障碍，表现为线粒体膜电位、ATP 产生、复合物 III 和柠檬酸合酶活性的显着降低。在此过程中，我们检测到线粒体动态显着受损，这反映在线粒体碎片显着增强上。一致地，我们还发现线粒体裂变的关键上游调节因子显着增强，例如短形式视神经萎缩1、动态相关蛋白1寡聚体和裂变1。线粒体OS或线粒体裂变的各自抑制可以相互减弱，从而显着防止线粒体功能障碍和细胞凋亡。总之，TEGDMA诱导的前成牙本质细胞凋亡是由线粒体OS和动态异常之间的恶性循环介导的，这为预防TEGDMA诱导的牙髓细胞凋亡提供了新的靶点。
Oxidative stress (OS) plays crucial roles in triethylene glycol dimethacrylate (TEGDMA, a major component in dental resin)-induced apoptosis of dental pulp cells. Mitochondria are important target organelles for regulating the balance of OS, meanwhile, imbalance of the mitochondrial dynamic associated with mitochondrial dysfunction is one major molecular mechanism for oxidative damages. However, whether these mitochondrial dependent pathways were involved in the apoptosis of dental pulp cells induced by TDGDMA remains unclarified. We demonstrated that TEGDMA decreased viability and induced apoptosis of mouse preodontoblasts (mDPC6T cell line) in a time-and dose-dependent manner. Furthermore, TEGDMA elevated the mitochondrial OS status and induced mitochondrial dysfunction, as reflected by the significant decrease of mitochondrial membrane potential, ATP production, the activity of Complex III and citrate synthase. In this process, we detected a dramatically impaired mitochondrial dynamic that was reflected by significantly enhanced mitochondrial fragmentation. Consistently, we also found a significant enhancement of the key upstream regulators for mitochondrial fission, such as short form of optic atrophy 1, dynamic related protein 1 oligomer and Fission 1. The respective inhibition of mitochondrial OS or mitochondrial fission could mutually attenuate each other, thereby significantly preventing both mitochondrial dysfunction and cell apoptosis. In conclusion, TEGDMA-induced preodontoblasts apoptosis was mediated by the vicious circle between mitochondrial OS and dynamic abnormality, which represented a new target to prevent TEGDMA-induced dental pulp cells apoptosis.