Endoplasmic Reticulum Stress Induced by Tunicamycin and Antagonistic Effect of Tiantai No.1(天泰1号) on Mesenchymal Stem Cells  

作　　者：吴正治 李映红 Andrew C.J.Huang 李明 张晓丽 王济国 杨敏 陈嫚茵 

机构地区：[1]Shenzhen Hospital of Southern Medical University [2]Larry Hillblom Islet Research Center,David Geffen School of Medicine,UCLA,Los Angeles,CA 90024,USA

出　　处：《Chinese Journal of Integrative Medicine》2010年第1期41-49,共9页中国结合医学杂志（英文版）

基　　金：Supported by the National Foundation of Traditional Chinese Medical Science and Technology(No.02-03LP41);Key Project of the Foundation of Science and Technology of Guangdong Province(No.2006B35630007)

摘　　要：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 mesenchymat 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 effeObjective： 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 mesenchymat 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 effe

关 键 词：endoplasmic reticulum stress Alzheimer＇s disease mesenchymal stem cell TUNICAMYCIN Tiantai No.1 

分 类 号：R96[医药卫生—药理学] R285[医药卫生—药学]