Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway.
OBJECTIVE
To investigate the mechanism of the action of estrogen, which stimulates the release of secreted amyloid precursor protein alpha (sAPP(alpha)) and decreases the generation of amyloid-beta protein (A(beta)), 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 sAPP(alpha) in a culture medium and the total amount of cellular amyloid precursor protein (APP) in neurons.


RESULTS
17beta-Estradiol (but not 17alpha-estradiol) and beta-estradiol 6-(O-carboxymethyl) oxime: BSA increased the secretion of sAPP(alpha) 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, 17beta-estradiol did not alter the synthesis of cellular APP.


CONCLUSIONS
The effect of 17beta-estradiol on sAPP(alpha) 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 sAPP(alpha) secretion.
Zhang
Sun
S
Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Huang
Ying
Y
Zhu
Yi-Chun
YC
Yao
Tai
T
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D009281:Naphthalenes; D010446:Peptide Fragments; D004958:Estradiol; D011493:Protein Kinase C; C058819:calphostin C