Chung Eun Young, Shin Soon Young, Lee Young Han
Institute of Molecular Life Science and Technology, Ewha Women's University, Seoul 120-750, South Korea.
Neurosci Lett. 2007 Jul 5;422(1):43-8. doi: 10.1016/j.neulet.2007.05.057. Epub 2007 Jun 7.
Astrocytes play important roles in guiding the construction of the nervous system, controlling extracellular ions and neurotransmitters, and regulating CNS synaptogenesis. Egr-1 is a transcription factor involved in neuronal differentiation and astrocyte cell proliferation. In this study, we investigated whether the tricyclic antidepressant (TCA) amitriptyline induces Egr-1 expression in astrocytes using rat C6 glioma cells as a model. We found that amitriptyline increased the expression of Egr-1 in a dose- and time-dependent manner. The amitriptyline-induced Egr-1 expression was mediated through serum response elements (SREs) in the Egr-1 promoter. SREs were activated by the Ets-domain transcription factor Elk-1 through the ERK and JNK mitogen-activated protein (MAP) kinase pathways. The inhibition of the ERK and JNK MAP kinase signals attenuated amitriptyline-induced transactivation of Gal4-Elk-1 and Egr-1 promoter activity. Our findings suggest that the induction of Egr-1 expression in astrocytes may be required to attain the therapeutic effects of antidepressant drugs.
星形胶质细胞在引导神经系统构建、控制细胞外离子和神经递质以及调节中枢神经系统突触形成中发挥着重要作用。Egr-1是一种参与神经元分化和星形胶质细胞增殖的转录因子。在本研究中，我们以大鼠C6胶质瘤细胞为模型，研究三环类抗抑郁药（TCA）阿米替林是否能诱导星形胶质细胞中Egr-1的表达。我们发现阿米替林以剂量和时间依赖性方式增加Egr-1的表达。阿米替林诱导的Egr-1表达是通过Egr-1启动子中的血清反应元件（SRE）介导的。Ets结构域转录因子Elk-1通过ERK和JNK丝裂原活化蛋白（MAP）激酶途径激活SRE。抑制ERK和JNK MAP激酶信号减弱了阿米替林诱导的Gal4-Elk-1反式激活和Egr-1启动子活性。我们的研究结果表明，星形胶质细胞中Egr-1表达的诱导可能是获得抗抑郁药物治疗效果所必需的。
