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Estrogen‐mediated neuroprotection against β‐amyloid toxicity requires expression of estrogen receptor α or β and activation of the MAPK pathway
Author(s) -
Fitzpatrick Jennifer L.,
Mize Amy L.,
Wade Christian B.,
Harris Julie A.,
Shapiro Robert A.,
Dorsa Daniel M.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01000.x
Subject(s) - estrogen receptor , estrogen , neuroprotection , chemistry , microbiology and biotechnology , mapk/erk pathway , phosphorylation , endocrinology , medicine , biology , pharmacology , cancer , breast cancer
It is well documented that estrogen can activate rapid signaling pathways in a variety of cell types. These non‐classical effects of estrogen have been reported to be important for cell survival after exposure to a variety of neurotoxic insults. Since direct evidence of the ability of the estrogen receptors (ERs) α and/or β to mediate such responses is lacking, the hippocampal‐derived cell line HT22 was stably transfected with either ERα (HTERα) or ERβ (HTERβ). In HTERα and HTERβ cells, but not untransfected cells, an increase in ERK2 phosphorylation was measured within 15 min of 17β‐estradiol treatment. The ER antagonist ICI 182, 780 (1 µ m ) and the MEK inhibitor, PD98059 (50 µ m ) blocked this increase in ERK2 phosphorylation. Treatment of HT22, HTERα and HTERβ cells with the β‐amyloid peptide (25–35) (10 µ m ) resulted in a significant decrease in cell viability. Pre‐treatment for 15 min with 10 n m 17β‐estradiol resulted in a 50% increase in the number of living cells in HTERα and HTERβ cells, but not in HT22 cells. Finally, ICI 182, 780 and PD98059 prevented 17β‐estradiol‐mediated protection. This study demonstrates that both ERα and ERβ can couple to rapid signaling events that mediate estrogen‐elicited neuroprotection.