Chinese Journal of Integrative Medicine

, Volume 16, Issue 1, pp 41–49

Endoplasmic reticulum stress induced by tunicamycin and antagonistic effect of Tiantai No.1 (天泰1号) on mesenchymal stem cells

  • Zheng-zhi Wu吴正治
  • Ying-hong Li李映红
  • Andrew C. J. Huang
  • Ming Li李 明
  • Xiao-li Zhang张晓丽
  • Ji-guo Wang王济国
  • Min Yang杨 敏
  • Man-yin Chen陈 茵
Experimental Research

DOI: 10.1007/s11655-010-0041-z

Cite this article as:
Wu, Z., Li, Y., Huang, A.C.J. et al. Chin. J. Integr. Med. (2010) 16: 41. doi:10.1007/s11655-010-0041-z

Abstract

Objective

Changes of the internal and external cellular environments can induce calcium homeostasis disorder and unfolded protein aggregation in the endoplasmic reticulum (ER). This ER function disorder is called endoplasmic reticulum stress (ERS). Severe long-term ERS can trigger the ER apoptosis signaling pathway, resulting in cell apoptosis and organism injury. Recent researches revealed that ERS-induced cell death was involved in the neurocyte retrogradation in the progress of neuron degenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease and so on. Therefore, the protection effect of the traditional Chinese drug—Tiantai No. 1 (天泰1号) on the ERS injury of AD was investigated at the molecular gene level in this study with a view to explore the gene pharmacodynamic actions and mechanisms of this drug.

Methods

Primarily cultured marrow mesenchymal stem cells (MSCs) of rats were treated by tunicamycin (TM) in order to induce ERS. RT-PCR, fluorescence immunocytochemistry and Western blot techniques were used to determine the mRNA and protein expression levels of the protective stress protein-ER molecular chaperones GRP78 and GRP94 (which would assist cells to resist cellular stress injury), and to determine the mRNA and protein expression levels of apoptosis promoting molecule Caspase-12 on the membrane of the ER, respectively.

Results

Protein expression levels of GRP78 and GRP94 were significantly increased in the TM-induced MSCs, and the mRNA level of Caspase-12 was also remarkably increased in the TM-induced MSCs (P<0.05). All these proved that the ERS model was successfully established by TM in MSC. Meanwhile, the mRNA and protein levels of GRP78 and GRP94 were all significantly increased compared with the model group (P<0.05 or P<0.01) after MSCs were treated with Tiantai No.1 while the mRNA and protein expression levels of Caspase-12 were significantly decreased compared with the model group (P<0.05 or P<0.01). This effect showed a dose dependent manner.

Conclusion

Tiantai No.1 might attenuate the cell apoptosis induced by ERS injury, and thus protect the neurons against AD.

Keywords

endoplasmic reticulum stressAlzheimer’s diseasemesenchymal stem celltunicamycinTiantai No.1

Copyright information

© Chinese Association of the Integration of Traditional and Western Medicine and Springer Berlin Heidelberg 2010

Authors and Affiliations

  • Zheng-zhi Wu吴正治
    • 1
  • Ying-hong Li李映红
    • 1
  • Andrew C. J. Huang
    • 2
  • Ming Li李 明
    • 1
  • Xiao-li Zhang张晓丽
    • 1
  • Ji-guo Wang王济国
    • 1
  • Min Yang杨 敏
    • 1
  • Man-yin Chen陈 茵
    • 1
  1. 1.Shenzhen Hospital of Southern Medical UniversityShenzhen, Guangdong ProvinceChina
  2. 2.Larry Hillblom Islet Research Center, David Geffen School of MedicineUCLALos AngelesUSA