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松果菊苷通过下调p53的表达抑制人成纤维细胞的衰老

朱慧, 成聪, 张弛, 王钊*   

  1. 1. 清华大学 医学院 生物科学与技术系 蛋白质科学教育部重点实验室, 北京 100084
    2. 北京市结核病胸部肿瘤研究所 药物研究室, 北京 101149
  • 收稿日期:2011-03-22 修回日期:2011-07-20 出版日期:2011-09-20 发布日期:2011-09-20
  • 通讯作者: 王钊*

Echinacoside suppresses cellular senescence of human fibroblastic cells by down-regulation of p53

Hui Zhu, Cong Cheng, Chi Zhang, Zhao Wang*   

  1. 1. Protein Science Key Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China
    2. Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
  • Received:2011-03-22 Revised:2011-07-20 Online:2011-09-20 Published:2011-09-20
  • Contact: Zhao Wang*

摘要:

松果菊苷是一种从肉苁蓉中分离得到的苯乙醇苷类化合物, 前期研究结果表明其有延缓人成纤维细胞衰老的作用。为了阐明松果菊苷抗衰老的机制, 我们对相关基因p53, p16, p21及Rb的mRNA及蛋白水平的表达进行了检测, 结果表明用松果菊苷处理后, 衰老的人成纤维细胞 (MRC-5) p53的表达被下调, 且呈剂量依赖方式。进一步的研究显示可能和SIRT1蛋白的上调有关。分子对接模拟结果显示松果菊苷的作用可能优于另一公认的抗衰老剂白藜芦醇。松果菊苷可能是一种潜在的可以调控细胞衰老的化合物。

关键词: 松果菊苷, 细胞衰老, p53, SIRT1

Abstract:

Echinacoside is one of the phenylethanoids isolated from the stems of Cistanches salsa. Our previous research showed that echinacoside has anti-senescence activity. To investigate the mechanism of echinacoside's anti-senescence activity, the expressions of p53, p21, p16 and Rb at the mRNA and protein levels were determined. Results showed that the expression of p53 was down-regulated significantly in a dose dependent manner after treatment with echinacoside. Further experiments suggested that the down-regulation of p53 may be correlated with the upregulation of SIRT1. In addition, echinacoside may exhibit considerable higher affinity towards SIRT1 than resveratrol, according to our molecular docking simulation. In conclusion, we expect that echinacoside might be a promising candidate for regulating cell senescence.

Key words: Echinacoside, Cellular senescence, p53, SIRT1

中图分类号: 

Supporting:

Foundation items: National Basic Research Program (973 Project) of China (Grant No. 2007CB507406), the National Natural Science Foundation of China (Grant No. 30572341) and the Tsinghua-Yue-Yuen Medical Sciences Fund (THYY20070008).
*Corresponding author: Tel.: 010-62772240; Fax: 86-10-62772675