神经保护
LY294002型
雌激素
雌激素受体
神经毒性
激酶
蛋白激酶B
谷氨酸受体
PI3K/AKT/mTOR通路
磷脂酰肌醇
药理学
化学
生物
信号转导
内分泌学
细胞生物学
内科学
医学
受体
生物化学
毒性
癌症
乳腺癌
作者
Kazuhiro Honda,Hideyuki Sawada,T Kihara,Makoto Urushitani,Tomoki Nakamizo,Akinori Akaike,Shun Shimohama
标识
DOI:10.1002/(sici)1097-4547(20000501)60:3<321::aid-jnr6>3.0.co;2-t
摘要
It has been shown that estrogen replacement in menopausal women is effective in slowing down the progression of cognitive impairment in Alzheimer's disease. Although recent studies have demonstrated the neuroprotective effects of estrogen, the precise mechanism of neuroprotection has not been elucidated. In the present study, we show that the phosphatidylinositol 3-kinase (PI3-K) cascade is involved in the neuroprotective mechanism stimulated by estrogen. Exposure to glutamate reduced the viability of rat primary cortical neurons. Pretreatment with 10 nM 17beta-estradiol significantly attenuated the glutamate-induced toxicity. This neuroprotective effect of 17beta-estradiol was blocked by co-administration with LY294002, a selective PI3-K inhibitor, but not by co-administration with PD98059, a selective mitogen activated protein kinase kinase inhibitor. Pretreatment with ICI182780, a specific estrogen receptor antagonist, also blocked the neuroprotection. Immunoblotting assay revealed that treatment with 17beta-estradiol induced the phosphorylation of Akt/PKB, an effector immediately downstream of PI3-K. These results suggest that PI3-K mediates the neuroprotective effect of 17beta-estradiol against glutamate-induced neurotoxicity.
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