Department of Neurology and Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, P. R. China.
Proteomics Clin Appl. 2009 Sep;3(9):1072-83. doi: 10.1002/prca.200800234. Epub 2009 Aug 26.
Glial-cell-line-derived neurotrophic factor (GDNF) is a potent survival factor for dopaminergic neurons, and hence serves as a therapeutic candidate for the treatment of Parkinson's disease. However, despite the potential clinical and physiological importance of GDNF, its mechanism of action is unclear. Therefore, we employed a state-of-the-art proteomic technique, DIGE, along with MS and a bioinformatics tool called Database for Annotation, Visualization and Integrated Discovery (DAVID), to profile proteome changes in the parkinsonian mouse striatum after GDNF challenge. Forty-six unique differentially expressed proteins were successfully identified, which were found either up-regulated and/or down-regulated at the two time points 4 and 72 h compared with the control. Proteins involved in cell differentiation and system development formed the largest part of the proteins regulated under GDNF. Furthermore, the aberrant expression of HSPs and mitochondria-associated proteins were noticeable. Moreover, mitochondrial stress 70 protein and heat shock cognate 71 kDa protein, whose relative levels increased significantly in GDNF-treated striatum, were further evaluated with Western blot and RT-PCR, demonstrating a good agreement with quantitative proteomic data. These data will provide some clues for understanding the mechanisms by which GDNF promotes the survival of dopaminergic neurons.
胶质细胞源性神经营养因子 (GDNF) 是多巴胺能神经元的一种有效存活因子，因此是治疗帕金森病的候选治疗药物。然而，尽管 GDNF 具有潜在的临床和生理重要性，但它的作用机制尚不清楚。因此，我们采用了最先进的蛋白质组学技术 DIGE 联合 MS 和一种名为 Database for Annotation, Visualization and Integrated Discovery (DAVID) 的生物信息学工具，来描绘 GDNF 作用于帕金森病小鼠纹状体后的蛋白质组变化。成功鉴定出了 46 种独特的差异表达蛋白，与对照组相比，这 46 种蛋白在 4 和 72 小时这两个时间点均呈现上调和/或下调。在 GDNF 调控下，细胞分化和系统发育相关蛋白构成了受调控蛋白的最大组成部分。此外，HSPs 和与线粒体相关的蛋白的异常表达也很明显。此外，GDNF 处理的纹状体中，线粒体应激 70 蛋白和热休克同源 71kDa 蛋白的相对水平显著增加，Western blot 和 RT-PCR 进一步验证了这一点，与定量蛋白质组学数据具有良好的一致性。这些数据将为理解 GDNF 促进多巴胺能神经元存活的机制提供一些线索。
