title: Aroclor1254 interferes with estrogen receptor-mediated neuroprotection against beta-amyloid toxicity in cholinergic SN56 cells.
abstract: Because estrogen plays important neurotrophic and neuroprotective roles in the brain by activating estrogen receptors (ERs), disruption of normal estrogen signaling can leave neurons vulnerable to a variety of insults, including β-amyloid peptide (Aβ). Aroclor1254 (A1254) belongs to the endocrine-disrupting chemical (EDC) polychlorinated biphenyls and has anti-estrogenic properties. In the present study, we evaluated the effect of A1254 on the protective activity of estrogen against Aβ toxicity in differentiated cholinergic SN56 cells. Aged Aβ25-35 causes apoptotic cell death in differentiated SN56 cells, and the cytotoxic evidences are effectively rescued by estrogen. We found that A1254 abolishes the neuroprotective activity of estrogen against Aβ toxicity, and attenuates the suppressive effect of estrogen on Aβ-induced tau phosphorylation and JNK activation. The effects of A1254 on the neuroprotective effects of estrogen in Aβ toxicity are very similar to the effects of the estrogen receptor antagonist ICI182,780. Thus, exposure to EDCs that have anti-estrogenic activity might interfere with normal estrogen-activated neuroprotective signaling events and leave neurons more vulnerable to dangerous stimuli. Our present results provide new understanding of the mechanisms contributing to the harmful effects of EDCs on the function and viability of neurons, and the possible relevance of EDCs in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Yeojin
authors.initials: Y
authors.lastname: Bang
authors.forename: Juhee
authors.initials: J
authors.lastname: Lim
authors.forename: Sa Suk
authors.initials: SS
authors.lastname: Kim
authors.forename: Hyung Min
authors.initials: HM
authors.lastname: Jeong
authors.forename: Ki-Kyung
authors.initials: KK
authors.lastname: Jung
authors.forename: Il-Hyun
authors.initials: IH
authors.lastname: Kang
authors.forename: Kwang-Youl
authors.initials: KY
authors.lastname: Lee
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Choi
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects*; D000077267:Fulvestrant; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D016875:tau Proteins; D020111:Chlorodiphenyl (54% Chlorine); D000077267:Fulvestrant; D004958:Estradiol; D007770:L-Lactate Dehydrogenase; D008156:Luciferases; C022616:thiazolyl blue