Effects of endoplasmic reticulum stress and related apoptosis on selective death of dopaminergic neurons

作     者：Lan Wang~, Shenggang Sun~, Xuebing Cao~, Zhentao Zhang~ and Li Xu~ Shenggang Sun Xuebing Cao Zhentao Zhang Li Xu 

作者机构：Department of Neurology Union Hospital Tongji Medical Collge Huazhong University of Science and Technlogy WuHan 430022China 

出 版 物：《Journal of Nanjing Medical University》 (南京医科大学学报（英文版）)

年 卷 期：2006年第20卷第4期

页      面：229-233页

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：National Natural Science Foundation of China(30570627) 

主　　题：endoplasmic reticulum stress apoptosis dopamine Parkinson's disease 

摘      要：Objective： To explore the mechanism of endoplasmic reticulum stress（ERS） response and related apoptosis in dopaminergic neurons death. Methods： Nerve growth factor （NGF）-treatedPC12 cells were treated with 6-OHDA, MPP^＋ and rotenone. MTT assay and flow cytometry were used to measure the cell viability and the rate of celluar apoptosis induced by those neurotoxins. The expression of ERS-related gene XBP1, Grp78, CHOP, caspase-12 in drug-treated group and reserpine preincubafion group was determined with RT-polymerase chain reaction（RT-PCR） and immunohistochemistry. Results： After the exposure to different toxins, the viability of PC12 cells were decreased by 52%, 44%, 40% at 100μM6-OHDA, 75 μM MPP^＋, 20 nM rotenone for 24 h respectively. FCM assay confirmed time-dependent cell apoptosis （P 〈 0.01 ）. The gene and protein expression of XBP1, Grp78 in drug-treated group were significantly increased and reached their peaks 8 h after the treatment（P 〈 0.05）. The expression levels of CHOP and caspase-12 gene were increased 16-24 h after the treatment（P 〈 0.01 ）, but the expression level of caspase-12 was inhibited by reserpine preincubayion（P 〈 0.05）. Conclusion： The excessive ERS and relative activated cell apoptosis pathway may be associated with selective death of dopaminergic neurons.