Corticosterone up-regulates expression and function of norepinephrine transporter in SK-N-BE(2)C cells.
Corticosterone up-regulates expression and function of norepinephrine transporter in SK-N-BE(2)C cells.
复制标题
皮质酮上调 SK-N-BE(2)C 细胞中去甲肾上腺素转运蛋白的表达和功能。
DOI：
10.1111/j.1471-4159.2010.06587.x
复制
发表时间：
2010
影响因子：
4.7
通讯作者：
Zhu,Meng-Yang
中科院分区：
文献类型：
--
作者：
Sun,Zhongwen;Fan,Yan;Zha,Qinqin;Zhu,Meng-Yang
J. Neurochem.(2010) 10.1111/j.1471‐4159.2010.06587.xAbstract 糖皮质激素通过调节应激期间许多基因的表达来影响大脑中的细胞和分子事件。在本研究中，我们在体外研究了皮质酮对去甲肾上腺素转运蛋白（NET）表达和功能的调节作用。结果表明，SK-N-BE(2)C 细胞暴露于皮质酮 14 天后，NET 的 mRNA（高达 43%）和蛋白质（高达 71%）水平以浓度依赖性方式显着增加。较长时间的暴露（21 天）导致 NET 的 mRNA 水平（高达约 160%）和蛋白质（高达约 250%）水平大幅增加。皮质酮对 NET 表达的上调作用在停止暴露后持续一段时间。与皮质酮诱导的 NET 表达增强相关，SK-N-BE(2)C 细胞对 [3H] 去甲肾上腺素的摄取也相应增加。将细胞暴露于皮质酮与米非司酮或螺内酯（两种皮质类固醇受体的特异性拮抗剂）组合后，增加的 NET 表达和功能被消除。这与皮质酮诱导的 NET 上调是由皮质类固醇受体介导的假设是一致的。然而，两种皮质类固醇受体拮抗剂的组合没有协同作用。将 PC12 细胞暴露于皮质酮后，也观察到类似的 NET 蛋白水平上调。目前的研究结果表明，皮质酮在体外上调 NET 的表达和功能，表明皮质酮对去甲肾上腺素能表型的作用可能在压力与抑郁症发展之间的相关性中发挥重要作用。
J. Neurochem.(2010) 10.1111/j.1471‐4159.2010.06587.xAbstractGlucocorticoids affect cellular and molecular events in brains by modulating the expression of many genes during stress. In the present study, we examined the regulatory effect of corticosterone on the expression and function of the norepinephrine transporter (NET)in vitro. The results show that exposure of SK‐N‐BE(2)C cells to corticosterone for 14 days significantly increased mRNA (up to 43%) and protein (up to 71%) levels of NET in the concentration‐dependent manner. Longer exposure (21 days) resulted in greater increases in the levels of mRNAs (up to about 160%) and proteins (up to about 250%) of the NET. The up‐regulatory effect of corticosterone on NET expression lasted a persistent period after cessation of exposure. Associated with the corticosterone‐induced enhancement in NET expression, there was a parallel increase in the uptake of [3H]norepinephrine by SK‐N‐BE(2)C cells. Increased NET expression and function were abolished after exposure of cells to corticosterone in combination with mifepristone or spironolactone, two specific antagonists of corticosteroid receptors. This is consistent with the hypothesis that corticosterone‐induced NET up‐regulation is mediated by corticosteroid receptors. Nevertheless, there was no synergistic effect for a combination of both corticosteroid receptor antagonists. A similar up‐regulation of NET protein levels was also observed after exposing PC12 cells to corticosterone. The present findings demonstrate that corticosterone up‐regulates the expression and function of NETin vitro, indicating the action of corticosterone on the noradrenergic phenotype may play an important role in the correlation between stress and the development of depression.