Cell death induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in AtT-20 pituitary cells.
The environmental man-made pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has profound and deleterious effects on the endocrine system, and the pituitary gland is among TCDD endocrine target organs. In the present study, we have investigated the effects of TCDD (1 pM, 0.1 nM and 1 nM) on the AtT-20 pituitary cell line. TCDD induces cell death, with morphological and biochemical changes indicating the occurrence of both apoptotic and necrotic cell death. Exposed cells exhibited apoptotic features including DNA condensation, activation of caspase-3 and exposure of phosphatidylserine (PS) on the outer plasma membrane. Concomitantly, cells with necrotic morphology such as cell swelling and plasma membrane damage were also present. The relative level of Fas ligand mRNA was increased after TCDD exposure, as well as Fas and Fas ligand protein levels detected by Western blotting and immunocytochemistry. Taken together, the results suggest that TCDD induces both necrosis and apoptosis in the pituitary AtT-20 cells and that the Fas/FasL system plays a critical role in inducing necrotic cell death rather than apoptosis (supported by the Swedish Research Council).
Huang
Ping
P
Division of Toxicology and Neurotoxicology, Institute of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden. ping.huang@imm.ki.se
Tofighi
Roshan
R
Emgard
Mia
M
Ceccatelli
Sandra
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009336:Necrosis; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor
D004785:Environmental Pollutants; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor