Role of mitogen-activated protein kinase cascades in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced apoptosis in neuronal pheochromocytoma cells.

Mitogen-activated protein kinases (MAPKs) are involved in neuronal death caused by many cytotoxins. Conventional MAPKs consist of three family members: extracellular signal-regulated kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38. It has been originally shown that ERK1/2 is important for cell survival, whereas JNK and p38 are deemed stress responsive and thus involved in apoptosis. However, information describing the role of MAPKs in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced neurotoxicity is insufficient. The aim of this study was to identify the role of MAPK cascades in TCDD-induced neurotoxicity using differentiated pheochromocytoma (PC12) cells as a model for neuronal cells. Cell viability assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and flow cytometry analysis showed that TCDD attenuated cell viability with a dose- and time-dependent manner and significantly induced apoptosis in primary cortical neurons and PC12 cells. Western blot analysis indicated t...