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Apolipoprotein E isoform‐specific disruption of phosphoinositide hydrolysis: protection by estrogen and glutathione
Author(s) -
Cedazo-Mı́nguez Angel,
Cowburn Richard F
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02761-2
Subject(s) - wortmannin , carbachol , endocrinology , estrogen , medicine , chemistry , apolipoprotein e , estrogen receptor , cholinergic , gene isoform , glutathione , muscarinic acetylcholine receptor , phosphatidylinositol , acetylcholine , microbiology and biotechnology , receptor , biochemistry , biology , signal transduction , enzyme , disease , cancer , breast cancer , gene
The mechanism(s) by which the E4 isoform of apolipoprotein E (apoE4) influences Alzheimer's disease (AD) are not fully known. We report that apoE4, but not apoE3, disrupts carbachol‐stimulated phosphoinositide (PI) hydrolysis in SH‐SY5Y neuroblastoma cells. Carbachol responses were also disrupted by β‐amyloid (Aβ) (1–42) and apoE4/Aβ(1–42) complexes, but not by apoE3/Aβ(1–42). Glutathione and estrogen protected against apoE4 and Aβ(1–42) effects, as well as those of H 2 O 2 . Estrogen protection was partially blocked by wortmannin, suggesting the involvement of phosphatidylinositol 3‐kinase. An apoE4‐induced disruption of acetylcholine muscarinic receptor‐mediated signalling may explain the lower effectiveness of cholinergic replacement treatments in apoE4 AD patients. Also, the beneficial effect of estrogen in AD may be partially due to its ability to protect against apoE4‐ and Aβ(1–42)‐mediated disruption of PI hydrolysis.