Open AccessEstrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway 1
Author(s) -
ZHANG Sun,
HUANG Ying,
ZHU Yichun,
YAO Tai
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00538.x
Subject(s) - amyloid precursor protein , protein kinase c , estrogen , medicine , secretion , calphostin c , endocrinology , p3 peptide , estrogen receptor , protein kinase a , chemistry , biology , microbiology and biotechnology , kinase , biochemistry , alzheimer's disease , disease , cancer , breast cancer
Abstract Aim: To investigate the mechanism of the action of estrogen, which stimulates the release of secreted amyloid precursor protein α (sAPPα) and decreases the generation of amyloid‐β protein (Aβ), a dominant component in senile plaques in the brains of Alzheimer's disease patients. Methods: Experiments were carried out in primary rat cortical neurons, and Western blot was used to detect sAPPα in a culture medium and the total amount of cellular amyloid precursor protein (APP) in neurons. Results: 17β‐Estradiol (but not 17α‐estradiol) and β‐estradiol 6‐( O ‐carboxymethyl) oxime: BSA increased the secretion of sAPPα and this effect was blocked by protein kinase C (PKC) inhibitor calphostin C, but not by the classical estrogen receptor antagonist ICI 182,780. Meanwhile, 17β‐estradiol did not alter the synthesis of cellular APP. Conclusion: The effect of 17β‐estradiol on sAPPα secretion is likely mediated through the membrane binding sites, and needs molecular configuration specificity of the ligand. Furthermore, the action of the PKC‐dependent pathway might be involved in estrogen‐induced sAPPα secretion.