title: Quantitative proteomics study of the neuroprotective effects of B12 on hydrogen peroxide-induced apoptosis in SH-SY5Y cells.
abstract: 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.
authors.affiliation: Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Juntuo
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Lou
authors.affiliation: Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xiajuan
authors.initials: X
authors.lastname: Zou
authors.affiliation: Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.|Beijing Key Laboratory of Tumor Systems Biology, Beijing, 100191, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003038:Cobamides / Q000494:pharmacology*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009447:Neuroblastoma / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003038:Cobamides; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D018696:Neuroprotective Agents; C450006:PTBP1 protein, human; D034741:RNA, Small Interfering; D038941:Polypyrimidine Tract-Binding Protein; D006861:Hydrogen Peroxide