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阻断MEK/ERK上调内质网应激条件下CHOP和p53表达 被引量：4

INHIBITION OF MEK UP-REGULATES THE EXPRESSION OF CHOP AND P53 UNDER ER STRESS
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摘要 目的:研究MEK/ERK信号途径在肝癌细胞SMMC-7721抵抗内质网应激诱导凋亡中的分子机制。方法:采用MEK特异抑制剂PD98059阻断内质网应激介导的MEK/ERK活化,并利用流式细胞和Western blot技术分析阻断MEK/ERK对内质网应激诱导的细胞凋亡及其关键调控分子GRP78、CHOP和p53表达的影响。结果:阻断MEK/ERK信号途径后,SMMC-7721细胞对内质网应激诱导凋亡的敏感性明显增强,CHOP和p53的蛋白水平显著上调。结论:内质网应激介导的MEK/ERK活化能够通过下调CHOP和p53表达抵抗细胞凋亡。 Objective： To investigate the molecular mechanism of MEK/ERK pathway in inhibiting ER stressinduced apoptosis of SMMC-7721 cells. Methods： MEK/ERK was blocked by MEK specific inhibitor PD98059, and its effects on ER stress-induced SMMC-7721 cells apoptosis and the expression of GRP78, CHOP and p53 wrer analyzed by flow cytometry and Western blot analysis. Results： SMMC-7721 cells were relatively resistant to ER stress-induced apoptosis. After MEK/ERK was blocked, SMMC-7721 cells were significantly sensitized to dithiothreitol- and thapsigargin-induced apoptosis. Furthermore,the block of MEK/ERK up-regulated the protein levels of CHOP and p53 in SMMC-7721 cells under ER stress. Conclusion： MEK/ERK pathway can inhibit ER stress-induced SMMC-7721 cells apoptosis through down-regwlating the protein levels of CHOP and p53.
作者 代荣阳 严冬梅 段春燕 李洪
机构地区 泸州医学院生物化学教研室
出处 《泸州医学院学报》 2009年第5期461-464,共4页 Journal of Luzhou Medical College
关键词 MEK/ERK信号途径 内质网应激 细胞凋亡 SMMC-7721 MEK/ERK pathway ER stress Cell apoptosis SMMC-7721
分类号 R735.7 [医药卫生—肿瘤] Q255 [生物学—细胞生物学]
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参考文献20

  • 1Schroder M, Kaufman RJ. ER stress and the unfolded protein response [J]. Mutat Res, 2005; 569:29.
  • 2Shen X, Zhang K, Kaufman RJ.The unfolded protein response: a stress signaling pathway of the endoplasmic reticulum [J]. J Chem Neuroanat, 2004;28:79.
  • 3Kaufman RJ. Stress signalling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls [J]. Genes Dev, 1999;13:1211.
  • 4Ma Y, Hendershot LM. The role of the unfolded protein response in tumour development: friend or foe [J]? Nat Rev Cancer, 2004;4:966.
  • 5Shuda M, Kondoh N, Imazeki N, et al. Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis [J]. J Hepatol, 2003;38:605.
  • 6Fernandez PM, Tabbara SO, Jacobs LK, et al. Overexpression of the glucose-regulated stress gene GRP78 in malignant but not benign human breast lesions [J]. Breast Cancer P,.es Treat, 2000;59:15.
  • 7Song MS, Park YK, regulated protein 78 tumor cells through signalling cascade [J]. Lee JH, et al. Induction of glucoseby chronic hypoxia in human gastric a protein kinase C-ε/ERK/AP-1 Cancer Res, 2001;61:8322.
  • 8Chen X, Ding Y, Liu CG, et al. Overexpression of glucose-regulated protein 94 (Grp94) in esophageal adenocarcinomas of a rat surgical model and humans [J]. Carcinogenesis, 2002;23:123.
  • 9Hu P, Han Z, Couvillon AD, et al. Critical role of endogenous Akt/IAPs and MEK1/ERK pathways in counteracting endoplasmic reticulum stress-induced cell death [J]. J Biol Chem, 2004;279:49420.
  • 10Yamasaki S, Yagishita N, Nishioka K, et al. The roles of synoviolin in crosstalk between endoplasmic reticulum stress-induced apoptosis and p53 pathway [J]. Cell Cycle, 2007;6:1319.

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泸州医学院学报
2009年 第5期

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