Estrogen effects on neurite outgrowth and cytoskeletal gene expression in ERα-transfected PC12 cell lines
Estrogen effects on neurite outgrowth and cytoskeletal gene expression in ERα-transfected PC12 cell lines
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DOI：
10.1006/exnr.2001.7744
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发表时间：
2001-10-01
影响因子：
5.3
通讯作者：
Oblinger, MM
中科院分区：
文献类型：
--
作者：
Gollapudi, L;Oblinger, MM
性腺类固醇如雌激素(E)促进神经突发芽的潜力在发育和衰老以及神经创伤后引起了人们的兴趣。两种主要雌激素受体Ella和ER β在神经元发芽中的具体作用尚不清楚。我们检验了E能以依赖内质网α的方式促进神经生长因子（NGF）刺激的神经突发芽的假设。将稳定转染全长大鼠内质网α基因（PCER）的PC12细胞与仅转染载体DNA （PCCON）的对照细胞进行比较。两种细胞系在神经生长因子作用下都能强烈分化神经突。我们确定这两种细胞系都显示ERP mRNA的基础表达，但只有PCER细胞表达Ella mRNA。雌激素处理显著增强了ngf刺激的PCER细胞的神经突生长，但对PCCON细胞没有作用。在E + NGF处理后，PCCON细胞中出现神经突的比例（24和48 h分别为34%和53%）明显高于PCCON细胞（24和48 h分别为17%和26%）。我们还研究了E和NGF对PCER和PCCON细胞外周蛋白、α -微管蛋白和tau mRNA表达的影响。在未分化的PCER细胞中，E处理增加了外周蛋白，降低了α -微管蛋白，并且没有改变tau mRNA的水平。对照组（未分化的PCCON细胞）在E处理后未观察到这些mrna的变化。NGF处理显著刺激PCER和PCCON细胞中外周蛋白、α -微管蛋白和tau mrna的表达。根据这些观察，我们得出结论，E与NGF协同作用，刺激神经突起发芽，并通过ER α调节几种细胞骨架mrna的表达。(C) 2001学术出版社。
The potential of gonadal steroids like estrogen (E) to promote neurite sprouting is of interest in development and aging, as well as after neural trauma. The specific roles of the two main estrogen receptors, Ella and ER beta, in neuronal sprouting are not yet well understood. We examined the hypothesis that E can enhance nerve growth factor (NGF)-stimulated neurite sprouting in an ER alpha -dependent manner. PC12 cells that were stably transfected with the full-length rat ER alpha gene (PCER) and a control line of cells transfected with vector DNA alone (PCCON) were compared. Both cell lines vigorously differentiate neurites when treated with NGF. We determined that both lines show basal expression of ERP mRNA, but only the PCER cells express Ella mRNA. Estrogen treatment markedly enhanced NGF-stimulated neurite outgrowth from PCER but not from PCCON cells. Significantly larger proportions of PCER cells (34 and 53% at 24 and 48 h, respectively) had neurites than did the PCCON cells (17 and 26% at 24 and 48 h) after E plus NGF treatment. We also examined the effects of E and NGF treatment of PCER and PCCON cells on peripherin, alpha -tubulin, and tau mRNA expression. In undifferentiated PCER cells, E treatment increased peripherin, reduced alpha -tubulin, and did not alter tau mRNA levels. No changes in these mRNAs were observed in the controls (undifferentiated PCCON cells) after E treatment. NGF treatment markedly stimulated expression of peripherin, alpha -tubulin, and tau mRNAs in both PCER and PCCON cells. From these observations we conclude that E synergizes with NGF and stimulates neurite sprouting and also modulates expression of several cytoskeletal mRNAs through ER alpha. (C) 2001 Academic Press.