JNK-mediated blockage of autophagic flux exacerbates the triethylene glycol dimethacrylate-induced mitochondrial oxidative damage and apoptosis in preodontoblast. (25th April 2021)

• Record Type: Journal Article
• Authors: Wang, Konghuai; Yu, Qihao; Wu, Danni; Liu, Ruona; Ren, Xuekun; Fu, Hui; Zhang, Xiaorong; Pan, Yihuai; Huang, Shengbin
• Is Part Of: Chemico-biological interactions. Volume 339(2021)
• Publication Date: 2021-04-25
• Subjects: TEGDMA -- Autophagy -- Oxidative stress -- Mitochondrial dysfunction -- Dental pulp cell -- Apoptosis; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2021.109432
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: 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. Highlights: TEGDMA induces autophagic flux blockage, mitochondrial oxidative damage and apoptosis in mDPC6T cells. TEGDMA-induced cytotoxicity is due to the blockage of autophagic flux. JNK-mediated blockage of autophagic flux causes the cytotoxicity of TEGDMA.