Tamoxifen protects clonal mouse hippocampal (HT-22) cells against neurotoxins-induced cell death.
In the present work using an established clonal mouse hippocampal (HT-22) cell line, we have examined whether the estrogen antagonist tamoxifen antagonizes the observed neuroprotective effects of estrogen against glutamate and amyloid beta protein neurotoxicity. Results obtained suggest that like estrogen, tamoxifen protects HT-22 cells against both 5mM glutamate and 2 microM amyloid beta protein induced cell death in a concentration dependent manner. Optimum protection was obtained at 500 nM tamoxifen. Tamoxifen was found to offer more potent protection at this dose against amyloid beta protein induced neurotoxicity when compared with glutamate neurotoxicity. We were unable to detect either estrogen receptor (ER)--ER alpha or ER beta presence in HT-22 cells using western blot technique. However, amyloid beta protein treatment significantly increases total glucocorticoid receptors (GRs) as determined by western blot technique, while prior treatment with estrogen or tamoxifen followed by amyloid beta protein resulted in the reduction of total GRs to the levels comparable to that observed for the control untreated cells. In addition, using confocal immunoflourescence microscopy technique, we observed that 20 h of treatment with 2 microM amyloid beta protein resulted in enhanced nuclear localization of GRs in HT-22 cells as compared to control untreated cells or 500 nM tamoxifen alone treated cells. Interestingly, 500 nM tamoxifen treatments for 24h, followed by 20 h treatment with 2 microM amyloid beta protein resulted in dramatic reduction in GRs nuclear localization. In conclusion, tamoxifen (i) protects HT-22 cells against amyloid beta protein neurotoxicity and (ii) neuroprotective effect is independent of ERs.
Gursoy
Erdal
E
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0551, USA.
Cardounel
Arturo
A
Al-khlaiwi
Thamir
T
Al-drees
Abdulmajeed
A
Kalimi
Mohammed
M
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D009498:Neurotoxins / Q000494:pharmacology*; D009994:Osmolar Concentration; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D004965:Estrogen Antagonists; D004967:Estrogens; D009498:Neurotoxins; D011965:Receptors, Glucocorticoid; D013629:Tamoxifen; D018698:Glutamic Acid