Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway
Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway作者机构:Department of Physiology and Pathophysiology Shanghai Medical College of FudanUniversity Shanghai 200032 China
出 版 物:《Acta Pharmacologica Sinica》 (中国药理学报(英文版))
年 卷 期:2005年第26卷第2期
页 面:171-176页
核心收录:
学科分类:1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学]
基 金:Project supported by the National Natural Science Foundation of China(№ 39970241)
主 题:Alzheimer disease estrogen amyloid precursor protein estrogen receptors protein kinase C
摘 要:Aim:To investigate the mechanism of the action of estrogen,which stimulates therelease of secreted amyloid precursor protein α(sAPPα)and decreases the gen-eration of amyloid-β protein(Aβ),a dominant component in senile plaques in thebrains of Alzheimer s disease ***:Experiments were carried out inprimary rat cortical neurons,and Western blot was used to detect sAPPα in aculture medium and the total amount of cellular amyloid precursor protein(APP)***:17β-Estradiol(but not 17α-estradiol)and β-estradiol 6-(O-carboxymethyl)oxime:BSA increased the secretion of sAPPα and this effect wasblocked by protein kinase C(PKC)inhibitor calphostin C,but not by the classicalestrogen receptor antagonist ICI 182,***,17β-estradiol did not alterthe synthesis of cellular ***:The effect of 17β-estradiol on sAPPαsecretion is likely mediated through the membrane binding sites,and needs mo-lecular configuration specificity of the ***,the action of the PKC-dependent pathway might be involved in estrogen-induced sAPPα secretion.