Pharmacologic effects of 2-methoxyestradiol on angiotensin type 1 receptor down-regulation in rat liver epithelial and aortic smooth muscle cells.
Pharmacologic effects of 2-methoxyestradiol on angiotensin type 1 receptor down-regulation in rat liver epithelial and aortic smooth muscle cells.
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DOI：
10.1016/j.genm.2012.01.008
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Thekkumkara T
中科院分区：
文献类型：
--
作者：
Koganti S;Snyder R;Thekkumkara T
女性心血管疾病的延迟发病还不清楚，但可能部分是由于绝经前雌激素的保护作用。实验研究已经确定血管紧张素1型受体（AT 1 R）是CVD进展的关键因素。在这项研究中，我们研究了雌激素代谢产物，2-甲氧基乙烯（2 ME 2），AT 1 R表达的影响。将大鼠肝细胞暴露于2 ME 2 24 h，并评估血管紧张素II（AngII）结合和AT 1 R mRNA表达。在2 ME 2的存在下，细胞表现出显著的下调AngII结合的剂量和时间依赖性的方式，不依赖于雌激素受体（ERα/ERβ）。AngII结合的下调是AT 1 R特异性的，受体亲和力没有变化。在相似的条件下，我们观察到AT 1 R mRNA的表达降低，显著抑制AngII介导的细胞内Ca 2+的增加，以及ERK 1/2磷酸化的增加。用MEK抑制剂PD 98059预处理细胞可阻止2 ME 2诱导的ERK 1/2磷酸化和AT 1 R表达下调，表明观察到的抑制作用是通过ERK 1/2信号中间体介导的。在具有组成型活性巨细胞病毒（CMV）启动子的稳定转染CHO细胞系中进行的类似分析显示，AT 1 R表达无变化，表明2 ME 2介导的作用是通过转录调控实现的。2 ME 2通过ERK 1/2对AT 1 R下调的作用在原代大鼠主动脉平滑肌细胞中一致地再现。由于AT 1 R在心血管疾病的控制中起着关键作用，2 ME 2诱导的受体表达的变化可能对心血管以及其他系统产生有益的影响。
Delayed onset of cardiovascular disease among females is not well understood, but could be in part due to the protective effect of estrogen before menopause. Experimental studies have identified the angiotensin type 1 receptor (AT1R) as a key factor in the progression of CVD. In this study, we examined the effects of the estrogen metabolite, 2-methoxyestradiol (2ME2), on AT1R expression. Rat liver cells were exposed to 2ME2 for 24 h and angiotensin II (AngII) binding and AT1R mRNA expressions were assessed. In the presence of 2ME2, cells exhibited significant down-regulation of AngII binding in a dose and time dependent manner, independent of estrogen receptors (ERα/ERβ). Down-regulation of AngII binding was AT1R specific with no change in receptor affinity. Under similar conditions, we observed lower expression of AT1R mRNA, significant inhibition of AngII mediated increase in intracellular Ca2+, and increased phosphorylation of ERK1/2. Pretreatment of cells with the MEK inhibitor PD98059 prevented 2ME2 induced ERK1/2 phosphorylation and down-regulation of AT1R expression, suggesting that the observed inhibitory effect is mediated through ERK1/2 signaling intermediate(s). Similar analyses in stably transfected CHO cell lines with a constitutively active cytomegalovirus (CMV) promoter showed no change in AT1R expression suggesting that 2ME2 mediated effects are through transcriptional regulation. The effect of 2ME2 on AT1R down-regulation through ERK1/2 were consistently reproduced in primary rat aortic smooth muscle cells. As AT1R plays a critical role in the control of cardiovascular diseases, 2ME2-induced changes in receptor expression may provide beneficial effects to the cardiovascular as well as other systems.
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DOI：
10.1161/hypertensionaha.110.152298
发表时间：
2010-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Barchiesi F;Lucchinetti E;Zaugg M;Ogunshola OO;Wright M;Meyer M;Rosselli M;Schaufelberger S;Gillespie DG;Jackson EK;Dubey RK
通讯作者：
Dubey RK
DOI：
10.1111/j.1471-0528.1981.tb02222.x
发表时间：
1981-01-01
期刊：
BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY
影响因子：
--
作者：
GERRETSEN, G;HUISJES, HJ;ELEMA, JD
通讯作者：
ELEMA, JD
影响因子：
3.6
作者：
Dahut, WL;Lakhani, NJ;Figg, WD
通讯作者：
Figg, WD
影响因子：
4.8
作者：
Bokkala, S;Joseph, SK
通讯作者：
Joseph, SK
DOI：
10.1530/acta.0.1000154
发表时间：
1982-01-01
期刊：
ACTA ENDOCRINOLOGICA
影响因子：
--
作者：
BERG, D;THALER, F;KUSS, E
通讯作者：
KUSS, E