Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway1

Authors

  • Sun ZHANG,

    1. Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai 200032, China;
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  • Ying HUANG,

    1. Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai 200032, China;
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  • Yi-chun ZHU,

    1. Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai 200032, China;
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  • Tai YAO

    Corresponding author
    1. Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai 200032, China;
    2. State Key Laboratory for Medical Neurobiology, Shanghai Medical College of Fudan University, Shanghai 200032, China
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  • 1

    Project supported by the National Natural Science Foundation of China (No 39970241).

Correspondence to Prof Tai YAO.
Ph n 86-21-6417-1179.
Fax 86-21-6417-1179 or 86-21-5423-7098.
E-mail tyao@shmu.edu.cn

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.

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