Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Endodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Endodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
Chem Biol Interact. 2021 Apr 25;339:109432. doi: 10.1016/j.cbi.2021.109432. Epub 2021 Mar 6.
Mitochondrial dependent oxidative stress (OS) and subsequent cell death are considered as the major cytotoxicity caused by Triethylene glycol dimethacrylate (TEGDMA), a commonly monomer of many resin-based dental composites. Under OS microenvironment, autophagy serves as a cell homeostatic mechanism and maintains redox balance through degradation or turnover of cellular components in order to promote cell survival. However, whether autophagy is involved in the mitochondrial oxidative damage and apoptosis induced by TEGDMA, and the cellular signaling pathways underlying this process remain unclear. In the present study, we demonstrated that TEGDMA induced mouse preodontoblast cell line (mDPC6T) dysfunctional mitochondrial oxidative response. In further exploring the underlying mechanisms, we found that TEGDMA impaired autophagic flux, as evidenced by increased LC3-II expression and hindered p62 degradation, thereby causing both mitochondrial oxidative damage and cell apoptosis. These results were further verified by treatment with chloroquine (autophagy inhibitor) and rapamycin (autophagy promotor). More importantly, we found that the JNK/MAPK pathway was the key upstream regulator of above injury process. Collectively, our finding firstly demonstrated that TEGDMA induced JNK-dependent autophagy, thereby promoting mitochondrial dysfunction-associated oxidative damage and apoptosis in preodontoblast.
线粒体依赖性氧化应激（OS）和随后的细胞死亡被认为是三甘醇二甲基丙烯酸酯（TEGDMA）引起的主要细胞毒性，TEGDMA 是许多树脂基牙科复合材料的常用单体。在 OS 微环境下，自噬作为一种细胞稳态机制，通过降解或转化细胞成分来维持氧化还原平衡，从而促进细胞存活。然而，自噬是否参与 TEGDMA 诱导的线粒体氧化损伤和细胞凋亡，以及该过程背后的细胞信号通路仍不清楚。在本研究中，我们证明了 TEGDMA 诱导小鼠前成牙本质细胞系（mDPC6T）功能失调的线粒体氧化反应。在进一步探索潜在机制时，我们发现 TEGDMA 损害了自噬流，这表现为 LC3-II 表达增加和 p62 降解受阻，从而导致线粒体氧化损伤和细胞凋亡。这些结果通过用氯喹（自噬抑制剂）和雷帕霉素（自噬促进剂）处理进一步得到验证。更重要的是，我们发现 JNK/MAPK 途径是上述损伤过程的关键上游调节剂。总之，我们的发现首次表明，TEGDMA 诱导 JNK 依赖性自噬，从而促进前成牙本质细胞中线粒体功能障碍相关的氧化损伤和凋亡。
