Angiotensin II-induced upregulation of AT1 receptor expression: sequential activation of NF-κB and Elk-1 in neurons
Angiotensin II-induced upregulation of AT1 receptor expression: sequential activation of NF-κB and Elk-1 in neurons
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DOI：
10.1152/ajpcell.00127.2010
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发表时间：
2010-09-01
影响因子：
5.5
通讯作者：
Zucker, Irving H.
中科院分区：
文献类型：
--
作者：
Mitra, Amit K.;Gao, Lie;Zucker, Irving H.
米特拉 AK，高 L，扎克 IH。血管紧张素 II 诱导的 AT(1) 受体表达上调：神经元中 NF-kappa B 和 Elk-1 的连续激活。 Am J Physiol Cell Physiol 299：C561-C569，2010。首次发表于 2010 年 6 月 16 日； doi: 10.1152/ajpcell.00127.2010.-已经明确，循环血管紧张素 II (ANG II) 的增加以及大脑和外周 ANG II 1 型受体 (AT(1)R) 的同时上调是多种以交感神经兴奋为特征的疾病的病理生理学中的重要介质。为了进一步了解神经元中 AT(1)R 表达的调节，我们确定了转录因子核因子 kappa B (NF-kappa B) 和 Ets 样蛋白 1 (Elk-1) 的连续激活在 AT(1)R 上调中的作用。我们用的是CATH。神经元作为我们的神经元细胞模型。在预设的时间过程中用 ANG II (100 nM) 处理细胞。 ANG II 激活后，NF-kappa B 的 p65 亚基暂时增加，在 30 分钟时观察到，在 1 小时达到峰值，并持续至 24 小时。 I kappa B 表达减少，I kappa K 表达增加。我们还观察到 AT(1)R 表达随着 NF-kappa B 的暂时增加而增加。使用抑制剂小白菊内酯或 p65 小干扰 RNA (siRNA) 阻断 NF-kappa B 的激活，这两种抑制剂都会导致 AT(1)R 表达减少。 Elk-1 的表达在 ANG II 激活后一段时间内上调，并在 NF-κ B 抑制后下降。使用电泳迁移率变动测定法评估 p65-DNA 结合，结果表明，存在时间依赖性增加的结合，而这种结合可通过小白菊内酯预处理或 siRNA 介导的 p65 基因沉默来抑制。因此，我们的结果表明转录因子 NF-kappa B 和 Elk-1 在 CATH 中 AT(1)R 上调中具有联合作用。细胞神经元模型。这些数据意味着正反馈机制可能会影响神经元对 ANG II 的放电敏感性。
Mitra AK, Gao L, Zucker IH. Angiotensin II-induced upregulation of AT(1)-receptor expression: sequential activation of NF-kappa B and Elk-1 in neurons. Am J Physiol Cell Physiol 299: C561-C569, 2010. First published June 16, 2010; doi: 10.1152/ajpcell.00127.2010.-It has been clearly established that increased circulating angiotensin II (ANG II) with concurrent upregulation of brain and peripheral ANG II type 1 receptors (AT(1)R) are important mediators in the pathophysiology of several diseases characterized by sympatho-excitation. In an effort to further understand the regulation of AT(1)R expression in neurons, we determined the role of sequential activation of the transcription factors nuclear factor-kappa B (NF-kappa B) and Ets-like protein 1 (Elk-1) in AT(1)R upregulation. We used CATH. a neurons as our neuronal cell model. Cells were treated with ANG II (100 nM) over a preset time course. Following ANG II activation, there was a temporal increase in the p65 subunit of NF-kappa B that was observed at 30 min, peaked at 1 h, and was sustained up to 24 h. There was a concomitant decrease of I kappa B and increased I kappa K expression. We also observed an increase in AT(1)R expression which followed the temporal increase of NF-kappa B. The activation of NF-kappa B was blocked by using the inhibitors parthenolide or p65 small interfering RNA (siRNA) which both led to a decrease in AT(1)R expression. The expression of Elk-1 was upregulated over a time period following ANG II activation and was decreased following NF-kappa B inhibition. p65-DNA binding was assessed using electrophoretic mobility shift assay, and it was shown that there was a time-dependent increased binding that was inhibited by means of parthenolide pretreatment or siRNA-mediated p65 gene silencing. Therefore, our results suggest a combined role for the transcription factors NF-kappa B and Elk-1 in the upregulation of AT(1)R in the CATH. a cell neuronal model. These data imply a positive feedback mechanism that may impact neuronal discharge sensitivity in response to ANG II.