Estradiol inhibits GSK3 and regulates interaction of estrogen receptors, GSK3, and beta-catenin in the hippocampus
Estradiol inhibits GSK3 and regulates interaction of estrogen receptors, GSK3, and beta-catenin in the hippocampus
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DOI：
10.1016/j.mcn.2003.10.008
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发表时间：
2004-03-01
影响因子：
3.5
通讯作者：
Wandosell, F
中科院分区：
文献类型：
--
作者：
Cardona-Gomez, P;Perez, M;Wandosell, F
雌激素调节一系列广泛的神经元功能，如基因表达、存活和分化，其方式与神经营养因子或生长因子的作用没有太大不同。研究得最好的激素作用是由雌激素受体介导的转录激活。然而，雌激素对生长因子信号的直接作用尚未明确。目前的数据表明，雌二醇在体内诱导成年雌性大鼠海马中GSK3的短暂激活，随后是更持久的抑制，这是由Tau磷酸化水平推断出来的。在接受激素治疗后，培养的海马神经元也获得了类似的数据。通过直接测定GSK3激酶活性证实了瞬时激活。此外，我们的研究结果显示了一种新的雌激素受体（x， GSK3和β -连环蛋白）复合物。激素的存在将-连环蛋白从这个复合体中移除。第二种复合体也受雌二醇影响，其中Tau与GSK3、β -连环蛋白和P13激酶复合体的元素相关。考虑到GSK3在神经退行性变中的作用，我们的数据表明雌激素的部分神经保护作用可能是由于GSK3的控制。(C) 2004爱思唯尔公司版权所有。
Estrogens regulate a wide set of neuronal functions such as gene expression, survival and differentiation in a manner not very different from that exerted by neurotrophins or by growth factors. The best-studied hormonal action is the transcriptional activation mediated by estrogen receptors. However, the direct effects of estrogen on growth factor signaling have not been well clarified.The present data show that estradiol, in vivo, induces a transient activation of GSK3 in the adult female rat hippocampus, followed by a more sustained inhibition, as inferred from phosphorylation levels of Tau. Similar data was obtained from cultured hippocampal neurons when treated with the hormone. The transient activation was confirmed by direct measure of GSK3 kinase activity.In addition, our results show a novel complex of estrogen receptor (x, GSK3, and beta-catenin. The presence of the hormone removes beta-catenin from this complex. There is a second complex, also affected by estradiol, in which Tau is associated with GSK3, beta-catenin, and elements of the P13 kinase complex. Considering the role of GSK3 in neurodegeneration, our data suggest that part of the neuroprotective effects of estrogen may be due to the control of GSK3. (C) 2004 Elsevier Inc. All rights reserved.