Genomic and non-genomic actions of estrogen on synaptic plasticity in SH-SY5Y cells
Genomic and non-genomic actions of estrogen on synaptic plasticity in SH-SY5Y cells
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DOI：
10.1016/j.neulet.2009.12.053
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发表时间：
2010-02-05
影响因子：
2.5
通讯作者：
Chongthammakun, Sukumal
中科院分区：
文献类型：
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作者：
Chamniansawat, Siriporn;Chongthammakun, Sukumal
雌激素调节突触可塑性，这是记忆存储的重要机制。此前，我们报道了雌激素通过非基因组磷酸肌醇3激酶（PI-3K）、丝裂原激活蛋白激酶（MAPK）和雌激素受体（ER）依赖性途径，在SH-SY5Y细胞中快速增加Arc（活性调节细胞骨架相关蛋白）的表达，Arc是突触可塑性的关键蛋白。本研究旨在研究每种 ER 亚型（α 和 β）在 SH-SY5Y 细胞突触可塑性中的作用。 ER β (DPN) 的特异性激动剂显着诱导 Arc 表达，类似于雌激素治疗。但不是 ER α (PTT)。使用免疫细胞化学测定 ER β 的亚细胞定位表明，ER β 保留在未处理细胞的细胞质中。在雌激素处理的细胞中，膜和胞质 ER β 逐渐减少，而核 ER β 以时间依赖性方式逐渐增加，表明 ER β 的核转位具有雌激素依赖性。雌激素处理后 6-12 小时，ERR 的核积累导致 PSD-95 和 SYP mRNA 表达增加，表明经典的基因组雌激素对突触可塑性的作用。然而，渥曼青霉素阻断 PI-3K 信号传导部分抑制了雌激素（48 小时）诱导的 PSD-95 和 SYP 表达，表明雌激素对突触可塑性的基因组和非基因组作用之间存在串扰机制。因此，雌激素增强的突触可塑性是ERβ依赖性的，并且涉及非基因组和基因组雌激素作用的串扰机制。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
Estrogen modulates synaptic plasticity, an important mechanism of memory storage. Previously, we have reported that estrogen rapidly increases the expression of Arc (activity-regulated cytoskeleton associated protein), a key protein for synaptic plasticity, via non-genomic phosphoinositide-3 kinase (PI-3K)-, mitogen-activated protein kinase (MAPK)-, and estrogen receptor (ER)-dependent pathways in SH-SY5Y cells. The present study aimed to investigate the role of each ER subtype, alpha and beta, in synaptic plasticity in SH-SY5Y cells. The specific agonist of ER beta (DPN) markedly induced Arc expression that mimics treatment with estrogen. but not ER alpha (PTT). Determination of subcellular localization of ER beta using immunocytochemistry shows that ER beta was retained in the cytoplasm of the untreated cells. In estrogen-treated cells, the membrane and cytosolic ER beta gradually decreased, while nuclear ER beta progressively increased in time-dependent manner, suggesting estrogen-dependent nuclear translocation of ER beta. Nuclear accumulation of ERR at 6-12 h post-estrogen treatment, leads to increased PSD-95 and SYP mRNA expression, indicating the classical genomic estrogenic action on synaptic plasticity. However, the block of PI-3K signaling by Wortmannin partially suppressed estrogen (48 h)-induced PSD-95 and SYP expression, suggesting a crosstalk mechanism between genomic and non-genomic actions of estrogen on synaptic plasticity. Therefore, the estrogen-enhanced synaptic plasticity is ER beta-dependent and involves the crosstalk mechanism of non-genomic and genomic estrogenic actions. (C) 2009 Elsevier Ireland Ltd. All rights reserved.