基础医学与临床 ›› 2016, Vol. 36 ›› Issue (8): 1035-1039.

• 研究论文 •    下一篇

硒通过核内积累IKK α诱导Jurkat细胞自噬依赖的caspase 8激活

史可鉴1,吴成爱1,王莹1,安佳佳2,杨洋3,田伟4   

  1. 1. 北京市创伤骨科研究所
    2. 滨州医学院附属医院
    3. 中国医学科学院基础医学研究所
    4. 北京积水潭医院
  • 收稿日期:2016-04-18 修回日期:2016-06-17 出版日期:2016-08-05 发布日期:2016-07-13
  • 通讯作者: 田伟 E-mail:wei_tian01@sina.com
  • 基金资助:
    国家自然科学基金重点项目;山东省优秀中青年科学家科研奖励基金

Selenite induced autophagy-dependent caspase 8 activation through accumulating IKK α in the nucleus of Jurkat cells

  • Received:2016-04-18 Revised:2016-06-17 Online:2016-08-05 Published:2016-07-13

摘要: 目的 重点探索超营养剂量的亚硒酸钠诱导白血病Jurkat细胞自噬和凋亡的分子机制。方法 Western blot实验,明确亚硒酸钠对IKK α、P73、UVRAG以及凋亡标志性蛋白天冬氨酸蛋白水解酶8(caspase 8)的表达及活性影响。用细胞转染技术,明确相关信号分子在Jurkat细胞死亡过程中发挥的作用。间接免疫荧光实验用于判断相关分子在细胞内的定位情况。结果 20μmol/L亚硒酸钠可有效促进Jurkat 细胞发生自噬和caspase 8相关的细胞凋亡(P<0.05),且caspase 8的活化依赖于细胞内的自噬水平(P<0.05)。此外,IKK α在细胞核内发生积累(P<0.05),进一步调节P73及自噬关键蛋白UVRAG的含量改变(P<0.05)。结论 超营养剂量的亚硒酸钠通过核内积累IKK α,诱导Jurkat细胞发生自噬依赖的caspase 8激活及凋亡。

关键词: 亚硒酸钠, 凋亡, 自噬, caspase 8, IKK α

Abstract: Objective The objective of our study is to explore the mechanisms by which selenite at super-nutritional range induced autophagy and apoptosis. Methods Western blot was used to detect the alteration of IKK α, P73, UVRAG and apoptotic markers(such as caspase 8) , while transfection assays were carried out to determine the essential role of signal molecules in regulating cell fate. Indirect immunofluorescent assay was used to judge the alteration of protein location. Results 20 μmol/L selenite promoted Jurkat cells undergoing caspase 8-related apoptosis and autophagy(P<0.05), while autophagy was necessary for the cleavage of caspase 8(P<0.05). Further experiments discovered that selenite regulated the contents of P73 and UVRAG(P<0.05), a maker of autophagy, through accumulating IKK α in the nucleus of Jurkat cells(P<0.05). Conclusions Super-nutritional selenite induced autophagy-dependent caspase 8 activation and apoptosis through accumulating IKK α in the nucleus.

Key words: Selenite, Apoptosis, Autophagy, caspase 8, IKK α

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