title: Role of mitogen-activated protein kinase cascades in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced apoptosis in neuronal pheochromocytoma cells.
abstract: 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 that TCDD markedly activated the expression of ERK1/2, JNK and p38 in TCDD-treated PC12 cells. Furthermore, PD98059 (ERK1/2 inhibitor), SP600125 (JNK inhibitor) and SB202190 (p38 inhibitor) notably blocked the effect of TCDD on cell apoptosis. Based on the findings above, it is concluded that the activation of MAPK signaling pathways may be associated with TCDD-mediated neuronal apoptosis.
authors.affiliation: 1Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: G
authors.initials: G
authors.lastname: Xu
authors.forename: Z
authors.initials: Z
authors.lastname: Duan
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Nie
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Wan
authors.forename: J
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000310:Adrenal Gland Neoplasms; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D010673:Pheochromocytoma; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D047428:Protein Kinase Inhibitors; D020928:Mitogen-Activated Protein Kinases
keywords: MAPKs; PC12; TCDD; apoptosis; primary cortical neurons