CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes
CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes
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DOI：
10.1016/j.bbrc.2011.05.065
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发表时间：
2011-06-17
影响因子：
3.1
通讯作者：
Shin, Chan Young
中科院分区：
文献类型：
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作者：
Kim, Ki Chan;Joo, So Hyun;Shin, Chan Young
在中枢神经系统损伤后，星形胶质细胞经历了一系列的生物学变化，包括增殖增加、炎性介质的产生和形态变化，这种反应统称为反应性胶质细胞增厚。这一过程是大脑对损伤反应的重要组成部分，然而，关于导致这些变化的分子机制(S)，人们还知之甚少。在本研究中，我们研究了胞浆多聚腺苷化元件结合蛋白1(CPEB1)在内毒素刺激的反应性胶质细胞增生性炎症反应中的调节作用。CPEB1是最近在星形胶质细胞中表达的一种mRNA结合蛋白，可能在星形胶质细胞的迁移中发挥作用。在脂多糖刺激下，大鼠原代星形胶质细胞中CPEB1的表达和磷酸化水平以JNK依赖的方式增加。SiRNA诱导的CPEB1表达下调抑制了内毒素诱导的iNOS的上调以及NO和ROS的产生，这是星形胶质细胞免疫激活的标志。研究结果表明，CPEB1积极参与星形胶质细胞炎症反应的调节，这可能为脑损伤后的调节机制提供新的见解。(C)2011 Elsevier Inc.保留所有权利。
Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury, yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury. (C) 2011 Elsevier Inc. All rights reserved.