Blockade of Cyclophilin D Attenuates Oxidative Stress-Induced Cell Death in Human Dental Pulp Cells

作者：Shengbin Huang, Bingbing Zheng, Xing Jin, Qihao Yu, Xiaorong Zhang, Xiaoyu Sun, Yuting Chen, Xuerui Ren, Daniël Wismeijer, Jianfeng Ma, Chengfei Zhang, Gang Wu, Yihuai Pan · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2019 · DOI：10.1155/2019/1729013 · 被引用次数：16 · 研究领域：Signaling Pathways in Disease、RNA Interference and Gene Delivery、Trace Elements in Health

Pathological stimuli, such as bacterial activity, dental bleaching, and nonpolymerized resin monomers, can cause death of dental pulp cells (DPCs) through oxidative stress- (OS-) induced mitochondrial dysfunction. However, the crucial molecular mechanisms that mediate such a phenomenon remain largely unknown. OS is characterized by the overproduction of reactive oxygen species (ROS), e.g., H 2 O 2 , O 2 − , and ⋅ OH. Mitochondria are a major source of ROS and the principal attack target of ROS. Cyclophilin D (CypD), as the only crucial protein for mitochondrial permeability transition pore (mPTP) induction, facilitates the opening of mPTP and causes mitochondrial dysfunction, leading to cell death. In the present study, we hypothesized that CypD-mediated mitochondrial molecular pathways were closely involved in the process of OS-induced death of human DPCs (HDPCs). We tested the phenotypic and molecular changes of HDPCs in a well-established OS model—H 2 O 2 treatment. We showed that H 2 O 2 dramatically reduced the viability and increased the death of HDPCs in a time- and dose-dependent manner by performing MTT, flow cytometry, and TUNEL assays and quantifying the expression changes of Bax and Bcl-2 proteins. H 2 O 2 also induced mitochondrial dysfunction, as reflected by the increased mitochondrial ROS, reduced ATP production, and activation of mPTP (decreased mitochondrial membrane potential and enhanced intracellular Ca 2+ level). An antioxidant (N-acetyl-L-cysteine) effe...