Fan Lu, Pandey Subhash C, Cohen Rochelle S
Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USA.
J Neurosci Res. 2008 Dec;86(16):3655-64. doi: 10.1002/jnr.21801.
The survival factor Bcl-2 is a cyclic AMP response element-binding protein (CREB) gene product implicated in mediating some of estrogen's effects on neuroprotection. Previously, we showed an effect of estradiol benzoate (E) on numbers of neuron-specific protein (NeuN)- and phosphorylated CREB (pCREB)-positive cells in medial (MeA), but not central (CeA), amygdala of ovariectomized rats. To determine whether these effects are accompanied by an E-induced increase in Bcl-2, we examined the effects of E on levels of Bcl-2 protein and mRNA in MeA and CeA of ovariectomized rats treated with E regimens resulting in moderate (2.5 microg E for 4 or 14 days) or high (10 microg E for 14 days) plasma estradiol levels. As a physiological control, we showed that all E treatments increased uterine wet weight relative to vehicle; 10 microg E for 14 days also increased uterine weight compared with that seen with lower E levels. Western blot analysis revealed that all E groups displayed an increase in uterine Bcl-2 protein levels compared with vehicle. We found that 2.5 microg and 10 microg E for 14 days increased levels of Bcl-2 gold immunolabeling compared with vehicle and 2.5 microg E for 4 days in MeA, but not CeA. We measured Bcl-2 mRNA levels in vehicle and 2.5 microg E-treated 14-day groups. There was a significant increase in Bcl-2 mRNA levels in MeA, but not CeA, of E-treated ovariectomized rats compared with vehicle controls. The E-induced increase in protein and mRNA levels of Bcl-2 in MeA may be important for neuroprotection in this region.
存活因子Bcl-2是一种环磷酸腺苷反应元件结合蛋白(CREB)基因产物,参与介导雌激素对神经保护的某些作用。此前,我们发现苯甲酸雌二醇(E)对去卵巢大鼠内侧杏仁核(MeA)而非中央杏仁核(CeA)中神经元特异性蛋白(NeuN)和磷酸化CREB(pCREB)阳性细胞的数量有影响。为了确定这些作用是否伴随着E诱导的Bcl-2增加,我们研究了E对接受导致中度(2.5μg E,持续4或14天)或高度(10μg E,持续14天)血浆雌二醇水平的E方案处理的去卵巢大鼠MeA和CeA中Bcl-2蛋白和mRNA水平的影响。作为生理对照,我们发现所有E处理组相对于溶剂对照组均增加了子宫湿重;与较低E水平相比,10μg E持续14天也增加了子宫重量。蛋白质免疫印迹分析显示,与溶剂对照组相比,所有E处理组子宫Bcl-2蛋白水平均升高。我们发现,与溶剂对照组和2.5μg E持续4天相比,2.5μg和10μg E持续14天增加了MeA中Bcl-2金免疫标记水平,但CeA中未增加。我们测量了溶剂对照组和2.5μg E处理14天组的Bcl-2 mRNA水平。与溶剂对照组相比,E处理的去卵巢大鼠MeA中Bcl-2 mRNA水平显著升高,但CeA中未升高。E诱导的MeA中Bcl-2蛋白和mRNA水平增加可能对该区域的神经保护很重要。