Original Articles

Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway

Sun ZHANG, Ying HUANG, Yi-chun ZHU, Tai YAO


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
Results: 17β-Estradiol (but not 17α-estradiol) and β-estradiol 6-(Ocarboxymethyl)
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 PKCdependent
pathway might be involved in estrogen-induced sAPPα secretion.