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An ICI 182,780‐Sensitive, Membrane‐Related Estrogen Receptor Contributes to Estrogenic Neuroprotective Actions against Amyloid‐Beta Toxicity
Author(s) -
MARTIN R,
GUERRA B,
MORALES A,
DÍAZ M,
ALONSO R
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1286.011
Subject(s) - neuroprotection , estrogen , toxicity , estrogen receptor beta , estrogen receptor , beta (programming language) , chemistry , amyloid (mycology) , pharmacology , medicine , endocrinology , computer science , cancer , breast cancer , inorganic chemistry , programming language
A bstract : Although estrogen (E2)‐related neuroprotection has been repeatedly demonstrated in different models, the involvement of non‐classical estrogen receptors (ERs) in this activity remains unclear. Using SN56 murine cholinergic cell line from the basal forebrain, we present evidence indicating that an ER associated with the plasma membrane participates in estrogen‐dependent reduction of neuronal death induced by amyloid‐β peptide (Aβ) toxicity. Exposure to either E2 or estradiol‐horseradish peroxidase (E‐HRP) for 15 min significantly reduced Aβ‐induced cell death. This effect was decreased by the ER antagonist ICI 182,780 as well as by MC‐20 antibody directed to a region neighboring the ligand‐binding domain of ERa. Using MC‐20 antibody in unpermeabilized SN56 cells, we detected a protein at the plasma membrane region. The binding of impermeant forms of E2, E‐HRP, and E‐BSA‐FITC to specific sites of SN56 plasma membrane was blocked by pre‐incubation with E2, ICI 182,780, and MC‐20 antibody in a concentration‐dependent manner. Thus, a membrane‐related ER that shares some structural homologies with ERα may participate in estrogen‐mediated neuroprotection.