Peroxiredoxin 5 prevents diethylhexyl phthalate-induced neuronal cell death by inhibiting mitochondrial fission in mouse hippocampal HT-22 cells

• Published in: Neurotoxicology (Park Forest South) 2019-09, Vol.74, p.242-251
• Main Authors: Lee, Dong Gil, Kim, Kyung-Min, Lee, Hyun-Shik, Bae, Yong Chul, Huh, Jae-Won, Lee, Sang-Rae, Lee, Dong-Seok
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Apoptosis; Apoptosis - genetics; Building materials; Cell death; Cell Death - genetics; Cell Line; Construction materials; Diethylhexyl phthalate; Diethylhexyl Phthalate - toxicity; Dioctyl phthalate; Fission; Gene Knockdown Techniques; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Mice; Mitochondria; Mitochondria - genetics; Mitochondria - ultrastructure; Mitochondrial dynamics; Mortality; Neurons - drug effects; Neurons - pathology; Neurotoxicity; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Perfumes; Peroxiredoxin; Peroxiredoxin 5; Peroxiredoxins - genetics; Peroxiredoxins - pharmacology; Phthalates; Reactive Oxygen Species; Therapeutic applications
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2019.08.003

•Diethylhexyl phthalate (DEHP) induces neurotoxicity through mitochondrial fission in HT-22 cells.•DEHP-induced oxidative stress triggers neuronal cell death via mitochondrial fission in HT-22 cells.•DEHP increases the expression levels of Peroxiredoxin 5 (Prx5).•Prx5 ameliorates DEHP-induced neurotoxicity by inhibiting mitochondrial fission. 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.