...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >TRPV4 regulates insulin mRNA expression and INS-1E cell death via ERK1/2 and NO-dependent mechanisms
【24h】

TRPV4 regulates insulin mRNA expression and INS-1E cell death via ERK1/2 and NO-dependent mechanisms

机译：TRPV4通过ERK1 / 2和无依赖机制调节胰岛素mRNA表达和INS-1E细胞死亡

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

TRPV4 is a Ca2+-permeable, nonselective cation channel. Recently, TRPV4 was implicated in controlling peripheral insulin sensitivity, insulin secretion and apoptosis of pancreatic beta cells. Here, we characterize the role and potential mechanisms of TRPV4 in regulating insulin mRNA expression and cell death in insulin producing INS-1E cells and rat pancreatic islets. TRPV4 protein production was downregulated by siRNA. Intracellular calcium level was measured using Fluo-3 AM. Gene expression was studied by real-time PCR. Phosphorylation of extracellular signal -regulated kinase (ERK1 and ERK2) was detected by Western blot. Nitric oxide (NO) production was assessed by chemiluminescent reaction. Reactive oxygen species (ROS) level was analysed using a fluorogenic dye (DCFDA). Cell death was evaluated by determination of cytoplasmic histone-associated DNA fragments. Downregulation of TRPV4 neither affected insulin mRNA expression nor INS-1E cell growth. By contrast, pharmacological TRPV4 activation by 100 nmo1/1 GSK1016790A increased Ca2+ levels in INS-1E cells and enhanced insulin mRNA expression after 1 and 3 h, whereas a suppression of insulin mRNA expression was detected after 24 h incubation. GSK1016790A increased ERK1/2 phosphorylation and NO production but not ROS production. Pharmacological blockade of ERK1/2 attenuated GSK1016790A-induced insulin mRNA expression. Inhibition of NO synthesis by L-NAME failed to affect insulin mRNA expression in GSK1016790A treated INS-1E cells. Furthermore, inhibition of NO production attenuated GSK1016790A-induced INS-1E cell death. In pancreatic islets, 100 nmo1/1 GSK1016790A increased insulin mRNA levels after 3 h without inducing cytotoxicity after 24 h.
机译：TRPV4是一种钙离子通透性强的非选择性阳离子通道。最近，TRPV4参与控制外周胰岛素敏感性、胰岛素分泌和胰腺β细胞凋亡。在这里，我们描述了TRPV4在胰岛素产生的INS-1E细胞和大鼠胰岛中调节胰岛素mRNA表达和细胞死亡的作用和潜在机制。TRPV4蛋白的产生被siRNA下调。使用Fluo-3 AM测量细胞内钙水平。基因表达通过实时PCR进行研究。Western blot检测细胞外信号调节激酶（ERK1和ERK2）的磷酸化。通过化学发光反应评估一氧化氮（NO）的产生。使用荧光染料（DCFDA）分析活性氧（ROS）水平。通过测定细胞质组蛋白相关DNA片段来评估细胞死亡。TRPV4的下调既不影响胰岛素mRNA的表达，也不影响INS-1E细胞的生长。相比之下，100 nmo1/1 GSK1016790A对TRPV4的药理学激活增加了INS-1E细胞中的Ca2+水平，并在1小时和3小时后增强了胰岛素mRNA的表达，而在培养24小时后检测到胰岛素mRNA的表达受到抑制。GSK1016790A增加ERK1/2磷酸化和NO生成，但不增加ROS生成。药物阻断ERK1/2可减弱GSK1016790A诱导的胰岛素mRNA表达。L-NAME抑制NO合成未能影响GSK1016790A处理的INS-1E细胞中胰岛素mRNA的表达。此外，抑制NO生成可减弱GSK1016790A诱导的INS-1E细胞死亡。在胰岛中，100 nmo1/1 GSK1016790A在3小时后增加胰岛素mRNA水平，而在24小时后不诱导细胞毒性。

著录项

  • 来源
    《Cellular Signalling》 |2017年第1期|共8页
  • 作者

    Billert M.; Skrzypski M.; Sassek M.; Szczepankiewicz D.; Wojciechowicz T.; Mergler S.; Strowski M. Z.; Nowak K. W.;

  • 作者单位

    Poznan Univ Life Sci Dept Anim Physiol &

    Biochem Wolynska 35 PL-60637 Poznan Poland;

    Poznan Univ Life Sci Dept Anim Physiol &

    Biochem Wolynska 35 PL-60637 Poznan Poland;

    Poznan Univ Life Sci Dept Anim Physiol &

    Biochem Wolynska 35 PL-60637 Poznan Poland;

    Poznan Univ Life Sci Dept Anim Physiol &

    Biochem Wolynska 35 PL-60637 Poznan Poland;

    Poznan Univ Life Sci Dept Anim Physiol &

    Biochem Wolynska 35 PL-60637 Poznan Poland;

    Charite Univ Med Berlin Dept Ophthalmol Berlin Germany;

    Charite Univ Med Berlin Dept Gastroenterol &

    Hepatol Interdisciplinary Ctr Metab Endocrinol Diabet &

    M D-13353 Berlin Germany;

    Poznan Univ Life Sci Dept Anim Physiol &

    Biochem Wolynska 35 PL-60637 Poznan Poland;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞形态学;
  • 关键词

    Beta-cell; Calcium; Insulin; Islets; TRPV4;

    机译：β细胞;钙;胰岛素;胰岛;TRPV4;

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