Estrogen effects in the myocardium:: Inhibition of NF-κB DNA binding by estrogen receptor-α and -β
Estrogen effects in the myocardium:: Inhibition of NF-κB DNA binding by estrogen receptor-α and -β
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DOI：
10.1006/bbrc.2001.5519
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发表时间：
2001-09-07
影响因子：
3.1
通讯作者：
Neyses, L
中科院分区：
文献类型：
--
作者：
Pelzer, T;Neumann, M;Neyses, L
我们之前已经证明，雌激素在心脏中的作用包括对心肌的直接激素作用。在最近的一项研究中，我们发现雌激素对心肌的一个有益作用是抑制心肌细胞的凋亡。这种作用与核因子-kappaB活性降低有关。在本研究中，我们分析了雌激素受体-α和-β抑制心肌中核因子-kappaB的作用机制。在培养的大鼠心肌细胞中，17-β-雌二醇(10 NM)抑制星形孢子素诱导的p65/p50核因子-kappaB复合体与其同源DNA元件的结合，但在星形孢子素或雌二醇作用下，心肌细胞提取物对p65、p50和I kappaB的表达或细胞定位没有影响。加入雌激素受体-α或雌激素受体-β作为重组蛋白，足以抑制星形孢菌素依赖的p65/p50DNA结合。17-β-雌二醇通过雌激素受体-α和-β抑制星形孢菌素诱导的p65/p50 DNA结合，与心肌细胞的凋亡性死亡相关。这与p65、p50和I kappaB表达的改变或亚细胞定位无关。因此，雌激素类化合物抑制核因子-kappaB活性可能会抑制心肌中促炎症细胞因子等依赖于核因子-kappaB的基因表达。(C)2001年学术出版社。
We have previously shown that estrogen effects in the heart include direct hormone effects on the myocardium. In a recent study we found that one beneficial effect of estradiol on the myocardium is the inhibition of apoptosis in cardiac myocytes. This effect was associated with a reduction of NF-kappaB activity. In the present study we have analyzed the functional mechanism of NF-kappaB inhibition in the myocardium by estrogen receptors-alpha and -beta. Despite the previous finding that 17-beta -estradiol (10 nM) inhibited the staurosporine-induced binding of p65/p50 NF-kappaB complexes to their cognate DNA elements in cultured rat cardiac myocytes, myocyte extracts showed no change in expression or cellular localization of p65, p50, and I kappaB upon staurosporine or estradiol treatment. Addition of either estrogen receptor-alpha or estrogen receptor-beta as recombinant protein was sufficient to inhibit staurosporine-dependent p65/p50 DNA binding in cardiac myocytes. 17-beta -Estradiol inhibits staurosporine-induced p65/p50 DNA binding associated with apoptotic cell death of cardiac myocytes via estrogen receptors-alpha and -beta. This is not associated with changes in p65, p50 and I kappaB expression or subcellular localization. Thus, inhibition of NF-kappaB activity by estrogenic compounds might inhibit NF-kappaB dependent gene expression such as proinflammatory cytokines in the myocardium. (C) 2001 Academic Press.