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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Project supported by the National Natural Science Foundation of China (No 39970241).
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Zhang, S., Huang, Y., Zhu, Yc. et al. Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway. Acta Pharmacol Sin 26, 171–176 (2005). https://doi.org/10.1111/j.1745-7254.2005.00538.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00538.x
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