The environmental estrogenic compound bisphenol A exerts estrogenic effects on mouse hippocampal (HT-22) cells: neuroprotection against glutamate and amyloid beta protein toxicity.
We have examined using immortalized clonal mouse hippocampal cell line (HT-22) whether the environmental estrogenic compound bisphenol A (BPA), like estrogen, has any neuroprotective effect against glutamate and amyloid beta protein-induced neurotoxicity. BPA protects HT-cells against both 5 mM glutamate and 2 microM amyloid beta protein-induced cell death in a dose dependent manner. Optimum protection was attained at 1 microM and 500 nM BPA against 5 mM glutamate and 2 microM amyloid beta protein-induced HT-22 cell death, respectively. Using confocal immunoflourescence microscopy technique, we observed that 20 h of treatment with 5 mM glutamate resulted in intense nuclear localization of the glucocorticoid receptors (GR) in HT-22 cells as compared to control untreated cells. Interestingly, 1 microM BPA treatment for 24 h, followed by 20-h treatment with 5 mM glutamate, resulted in dramatic reduction in GR nuclear localization. We conclude that: (i) BPA mimics estrogen and exerts neuroprotective effects against both neurotoxins used; (ii) BPA inhibits enhanced nuclear localization of GR induced by glutamate; and (iii) HT-22 cells provide a good in vitro model system for screening the potencies of various environmental compounds for their estrogenic activity.
Gursoy
E
E
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0551, USA.
Cardounel
A
A
Kalimi
M
M
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000506:poisoning*; D000818:Animals; D001559:Benzhydryl Compounds; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000506:poisoning*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects; D000098826:Bisphenol A Compounds
D016229:Amyloid beta-Peptides; D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010636:Phenols; D011965:Receptors, Glucocorticoid; C006780:bisphenol A; D000098826:Bisphenol A Compounds