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Phosphatidylinositol 3‐kinase mediates neuroprotection by estrogen in cultured cortical neurons
Author(s) -
Honda Kazuhiro,
Sawada Hideyuki,
Kihara Takeshi,
Urushitani Makoto,
Nakamizo Tomoki,
Akaike Akinori,
Shimohama Shun
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(20000501)60:3<321::aid-jnr6>3.0.co;2-t
Subject(s) - neuroprotection , ly294002 , estrogen , estrogen receptor , neurotoxicity , kinase , protein kinase b , glutamate receptor , pi3k/akt/mtor pathway , phosphatidylinositol , pharmacology , chemistry , biology , signal transduction , endocrinology , microbiology and biotechnology , medicine , receptor , biochemistry , toxicity , cancer , breast cancer
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 17β‐estradiol significantly attenuated the glutamate‐induced toxicity. This neuroprotective effect of 17β‐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 17β‐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 17β‐estradiol against glutamate‐induced neurotoxicity. J. Neurosci. Res. 60:321–327, 2000 © 2000 Wiley‐Liss, Inc.