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中国药学(英文版) ›› 2014, Vol. 23 ›› Issue (11): 772-777.DOI: 10.5246/jcps.2014.11.098

• 【研究论文】 • 上一篇    下一篇

氯化钆对PKC的激活可促进成纤维细胞NIH3T3的存活及细胞周期的推进

冯敏, 李金霞, 马孝杰, 范云周, 吴竞轩, 曾群, 杨晓改*   

  1. 北京大学药学院 化学生物学系, 北京 100191 
  • 收稿日期:2014-05-20 修回日期:2014-05-29 出版日期:2014-11-24 发布日期:2014-06-06
  • 通讯作者: Tel.: 86-10-82805956
  • 基金资助:
    National Natural Science Foundation of China (Grant No. 21277006 and 20637010).

The involvement of signaling activation of protein kinase C in gadolinium chloride-induced cell survival and cell cycle progression in NIH3T3 cells

Min Feng, Jinxia Li, Xiaojie Ma,Yunzhou Fan, Jingxuan Wu, Qun Zeng, Xiaogai Yang*   

  1. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2014-05-20 Revised:2014-05-29 Online:2014-11-24 Published:2014-06-06
  • Contact: Tel.: 86-10-82805956
  • Supported by:
    National Natural Science Foundation of China (Grant No. 21277006 and 20637010).

摘要:

本研究以氯化钆为代表性含稀土元素的化合物, 在小鼠胚胎成纤维细胞NIH3T3蛋白激酶C家族蛋白的激活进行了研究。利用活细胞成像和共聚焦激光扫描技术可以观察到, 在血清饥饿的条件下, 50 μM的氯化钆可以通过增强细胞粘附和细胞骨架重组促进细胞存活。使用蛋白质印迹技术发现蛋白激酶C家族蛋白在氯化钆作用不同时间后可以发生磷酸化, 表明蛋白激酶C被激活。此外, 双吲哚马来酰亚胺(bisindolylmaleimide, 一种PKCpan的抑制剂)可以有效降低PKCpan磷酸化的水平(βIISer660), 同时也可以降低氯化钆引起的ERK的激活。以上结果表明, 氯化钆激活的蛋白激C可以通过介导MAPK/ERK信号通路的激活, 继而推动细胞周期和细胞存活。

关键词: 氯化钆, 细胞周期, 蛋白激酶C, 细胞骨架, ERK, NIH3T3细胞

Abstract:

In the present study, we investigated the activation of protein kinase C (PKC) family in mouse embryonic fibroblast NIH3T3 cells using gadolinium chloride as a representative lanthanide ion. With live cell imaging system and confocal laser scanning microscopy, we found that the treatment of 50 μM GdCl3 promoted cell survival under the condition of serum-starvation. Moreover, better cell attachment and cytoskeleton reorganization were also observed. Additionally, GdCl3 treatment resulted in the phosphorylation of PKC family at different time points. Furthermore, bisindolylmaleimide (a PKCpan inhibitor) could efficiently reduce the level of phosphorylated PKCpan (βIISer660), alleviating ERK activation induced by GdCl3. This finding indicated that the PKC activation was involved in GdCl3-induced MAPK/ERK signaling and thus might contribute to GdCl3-induced cell cycle progression and cell survival.

Key words: Gadolinium chloride, Cell cycle, Protein kinase C, Cytoskeleton, ERK, NIH3T3 cells

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