School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
Neurotoxicology. 2019 Sep;74:242-251. doi: 10.1016/j.neuro.2019.08.003. Epub 2019 Aug 10.
Diethylhexyl phthalate (DEHP) is used in many plastic products, such as perfumes, lunch boxes, bags, and building materials. As DEHP is not covalently bound to the plastic, humans can be easily exposed to it. DEHP induces neurobehavioral changes and neuronal cell death; however, the exact mechanism behind this is still unclear. We hypothesized that the neurotoxic mechanism is related to DEHP-induced oxidative stress leading to apoptosis through mitochondrial fission. We demonstrated that DEHP-induced oxidative stress triggers neuronal cell death via mitochondrial fission in mouse hippocampal HT-22 cells. Furthermore, we identified that peroxiredoxin 5 (Prx5), an antioxidant enzyme induced by DEHP, prevents DEHP-induced mitochondrial fission by inhibiting the production of reactive oxygen species. We conclude that Prx5 may be a promising therapeutic target for mitigating DEHP-induced neuronal cell death.
邻苯二甲酸二乙酯（DEHP）用于许多塑料制品中，如香水、午餐盒、袋子和建筑材料。由于 DEHP 与塑料没有共价结合，因此人类很容易接触到它。DEHP 会引起神经行为改变和神经元细胞死亡；然而，其背后的确切机制尚不清楚。我们假设神经毒性机制与 DEHP 诱导的氧化应激有关，通过线粒体裂变导致细胞凋亡。我们证明 DEHP 诱导的氧化应激通过线粒体裂变触发小鼠海马 HT-22 细胞中的神经元细胞死亡。此外，我们发现 DEHP 诱导的抗氧化酶过氧化物酶 5（Prx5）通过抑制活性氧的产生来防止 DEHP 诱导的线粒体裂变。我们得出结论，Prx5 可能是减轻 DEHP 诱导的神经元细胞死亡的有前途的治疗靶点。
