...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Proteomic analysis of lithium-induced nephrogenic diabetes insipidus: Mechanisms for aquaporin 2 down-regulation and cellular proliferation
【24h】

Proteomic analysis of lithium-induced nephrogenic diabetes insipidus: Mechanisms for aquaporin 2 down-regulation and cellular proliferation

机译：锂致尿崩症的蛋白质组学分析：水通道蛋白2下调和细胞增殖的机制。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Lithium is a commonly prescribed mood-stabilizing drug. However, chronic treatment with lithium induces numerous kidney-related side effects, such as dramatically reduced aquaporin 2 (AQP2) abundance, altered renal function, and structural changes. As a model system, inner medullary collecting ducts (IMCD) isolated from rats treated with lithium for either 1 or 2 weeks were subjected to differential 2D gel electrophoresis combined with mass spectrometry and bioinformatics analysis to identify (ⅰ) signaling pathways affected by lithium and (ⅱ) unique candidate proteins for AQP2 regulation. After 1 or 2 weeks of lithium treatment, we identified 6 and 74 proteins with altered abundance compared with controls, respectively. We randomly selected 17 proteins with altered abundance caused by lithium treatment for validation by immunoblotting. Bioinformatics analysis of the data indicated that proteins involved in cell death, apoptosis, cell proliferation, and morphology are highly affected by lithium. We demonstrate that members of several signaling pathways are activated by lithium treatment, including the PKB/Akt-kinase and the mitogen-activated protein kinases (MAPK), such as extracellular regulated kinase (ERK), c-Jun NH_2-terminal kinase(JNK), and p38. Lithium treatment increased the intracellular accumulation of β-catenin in association with increased levels of phosphorylated glycogen synthase kinase type 3β (GSK3β). This study provides a comprehensive analysis of the proteins affected by lithium treatment in the IMCD and, as such, provides clues to potential lithium targets in the brain.
机译：锂是一种常用的稳定情绪的药物。但是，长期用锂治疗会引起许多肾脏相关的副作用，例如水通道蛋白2（AQP2）的丰度大大降低，肾脏功能改变和结构改变。作为模型系统，将从锂处理1周或2周的大鼠中分离出的髓内集管（IMCD）进行差分2D凝胶电泳，结合质谱和生物信息学分析，以识别（ⅰ）受锂影响的信号通路和（ ⅱ）用于AQP2调控的独特候选蛋白。锂处理1或2周后，我们分别确定了6种和74种蛋白质的丰度与对照组相比发生了变化。我们随机选择了由锂处理引起的丰度改变的17种蛋白质，以进行免疫印迹验证。数据的生物信息学分析表明，与细胞死亡，细胞凋亡，细胞增殖和形态有关的蛋白质受锂的影响很大。我们证明锂处理激活了几个信号通路的成员，包括PKB / Akt激酶和丝裂原激活的蛋白激酶（MAPK），例如细胞外调节激酶（ERK），c-Jun NH_2-末端激酶（JNK） ）和p38。锂处理增加了β-catenin的细胞内积累，并伴有3β型磷酸化糖原合酶激酶（GSK3β）水平的升高。这项研究提供了对IMCD中受锂处理影响的蛋白质的全面分析，因此，它为大脑中潜在的锂靶标提供了线索。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号