<i>p,p</i>′‑DDE Induces Apoptosis through the Modulation of Tumor Necrosis Factor α in PC12 Cells

Abstract

<i>p,p</i>′-DDE, the main metabolite of DDT, is notorious for its persistent and bioaccumulation. It has detrimental effects on the nervous system, while the mechanism is unclear. We sought to investigate the mechanism of <i>p,p</i>′-DDE-induced neurocytic apoptosis in PC12 cells by cytoflow and screen the potential target gene by microarray and ELISA. Co-incubation with antagonist and SiRNA were applied to confirm the effect of the selected molecular. Results were also confirmed in zebrafish embryo. Results showed that <i>p,p</i>′-DDE induced apoptosis in PC12 cells at a concentration of ≥2 × 10^–5 mol/L. Microarray results indicate that the TNF family plays a key role in <i>p,p</i>′-DDE-induced apoptosis among 84-apoptotic genes. In particular, the protein level of TNFα increased 4-fold. When incubated with TNFα antibody (infliximab), the number of apoptotic cells attenuated by 50%, and both activities of caspases 8 and 9 decreased. SiRNA silencing of TNFα showed similar trends. Furthermore, <i>p,p</i>′-DDE induced neuronal apoptosis in zebrafish embryos in a dose-dependent manner.This effect was partially reversed by infliximab, too. Overall, the present study herein indicated that the TNFα signaling pathway is involved in <i>p,p</i>′-DDE-induced neurocyte apoptosis. These data could be expanded to other cases of OCP-induced apoptosis and would support the need for scientific intervention to address the neurotoxicity of these chemicals