Quantitative proteomics study of the neuroprotective effects of B12 on hydrogen peroxide-induced apoptosis in SH-SY5Y cells.
Quantitative proteomics study of the neuroprotective effects of B12 on hydrogen peroxide-induced apoptosis in SH-SY5Y cells.
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DOI：
10.1038/srep22635
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发表时间：
2016-03-08
影响因子：
4.6
通讯作者：
Pan Y
中科院分区：
文献类型：
--
作者：
Zhong L;Zhou J;Chen X;Lou Y;Liu D;Zou X;Yang B;Yin Y;Pan Y
B12属于香豆素类化合物，已显示具有各种生理和药理活性，包括抗炎、抗菌和抗氧化剂。在本研究中，我们的特点是神经保护作用的B12对H2 O2诱导的神经元细胞损伤SH-SY 5 Y细胞。蛋白质表达谱结合途径分析，部署在人类神经元细胞中的神经保护作用，使用无标记的定量蛋白质组学方法研究相关的分子事件。共22个蛋白质显着差异表达在H2 O2损伤细胞与B12处理或不处理。使用Celloscape平台进行的生物信息学分析表明，聚嘧啶段结合蛋白1（PTBP 1）与保护作用高度相关，蛋白质印迹证实，与H2 O2处理组相比，H2 O2 + B12处理组中PTBP 1上调。PTBP RNAi实验敲低了PTBP的表达，这抵消了B12对细胞活力的保护作用。因此，我们推断，B12的神经保护活性涉及上调PTBP 1及其相关的信号网络H2 O2诱导SH-SY 5 Y细胞凋亡。B12或相关化合物可被证明是用于治疗神经变性疾病如阿尔茨海默氏病和帕金森氏病的有用治疗剂。
B12 belongs to the coumarin class of compounds that have been shown to have various physiological and pharmacological activities including anti-inflammatory, antibacterial, and antioxidant. In the present study, we characterised the neuroprotective effects of B12 against H2O2-induced neuronal cell damage in SH-SY5Y cells. Protein expression profiling in combination with pathway analysis was deployed to investigate the molecular events associated with the neuroprotective effects in human neuronal cells using a label-free quantitative proteomics approach. A total of 22 proteins were significantly differentially expressed in H2O2-damaged cells with or without B12 treatment. Bioinformatics analysis using the Cytoscape platform indicated that poly pyrimidine tract binding protein 1 (PTBP1) was highly associated with the protective effect, and western blotting verified that PTBP1 was up-regulated in H2O2 + B12 treatment group, compared with the H2O2 treated group. PTBP RNAi experiments knocked down PTBP expression, which cancelled out the protective effect of B12 on cell viability. Thus, we infer that B12 neuroprotective activity involves up-regulation of PTBP1 and its associated signalling networks following H2O2-induced apoptosis in SH-SY5Y cells. B12 or related compounds may prove to be useful therapeutic agents for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s.