Document Detail

Aroclor1254 interferes with estrogen receptor-mediated neuroprotection against beta-amyloid toxicity in cholinergic SN56 cells.
MedLine Citation:
PMID:  21693151     Owner:  NLM     Status:  MEDLINE    
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.
Yeojin Bang; Juhee Lim; Sa Suk Kim; Hyung Min Jeong; Ki-Kyung Jung; Il-Hyun Kang; Kwang-Youl Lee; Hyun Jin Choi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-13
Journal Detail:
Title:  Neurochemistry international     Volume:  59     ISSN:  1872-9754     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-19     Completed Date:  2012-01-12     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  582-90     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea.
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MeSH Terms
Amyloid beta-Peptides / antagonists & inhibitors,  toxicity*
Blotting, Western
Cell Differentiation / drug effects
Cell Line, Tumor
Chlorodiphenyl (54% Chlorine) / pharmacology*
Estradiol / analogs & derivatives,  pharmacology
Estrogen Antagonists* / pharmacology
Estrogen Receptor alpha / drug effects*
In Situ Nick-End Labeling
L-Lactate Dehydrogenase / metabolism
Luciferases / metabolism
Mice, Inbred C57BL
Microscopy, Fluorescence
Neuroprotective Agents / metabolism,  pharmacology*
Parasympathetic Nervous System / cytology*,  drug effects
Tetrazolium Salts
tau Proteins / metabolism
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Estrogen Antagonists; 0/Estrogen Receptor alpha; 0/Neuroprotective Agents; 0/Tetrazolium Salts; 0/Thiazoles; 0/tau Proteins; 11097-69-1/Chlorodiphenyl (54% Chlorine); 22X328QOC4/fulvestrant; 298-93-1/thiazolyl blue; 50-28-2/Estradiol; EC Dehydrogenase; EC 1.13.12.-/Luciferases

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