title: Protective action of 17beta-estradiol and tamoxifen on glutamate toxicity in glial cells.
abstract: Estrogens influence differentiation, growth and function of neurons, but less is known of their effects on glia. In our experiments reported here, the ovarian steroid, 17beta-estradiol, and the "designer", non-steroidal estrogen, tamoxifen, effectively protected C-6 glioma 2B clone cells from the cytotoxicity of the excitatory neurotransmitter, glutamate. Exposure of these cells to 10-20 mM glutamate induced 61-78% cell death. Pre-treatment of the cells with 0.01 mM estradiol or with 2 microM tamoxifen significantly reduced the glutamate-induced cell death, estradiol being the most effective in this regard. Estradiol- or tamoxifen-treated cells that had survived glutamate damage appeared more mature than controls. Thus, estrogens often used in therapy (estradiol as replacement after menopause and tamoxifen for treatment/prevention of breast cancer) may significantly protect glial cells against glutamate toxicity and stimulate cell differentiation.
authors.affiliation: Department of Molecular Biology, University of California, 410 Barker Hall, Berkeley, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Shy
authors.forename: L
authors.initials: L
authors.lastname: Malaiyandi
authors.forename: P S
authors.initials: PS
authors.lastname: Timiras
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005910:Glioma; D018698:Glutamic Acid / Q000633:toxicity*; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
chemical_list: D004965:Estrogen Antagonists; D013629:Tamoxifen; D018698:Glutamic Acid; D004958:Estradiol