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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.
Highlights
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
Cell proliferation was observed in SH-SY5Y cells after treatment with H2O2 at a range of doses, and cell number decreased with increasing H2O2 concentration
A recent study by King et al.[19] showed that pyrimidine tract binding protein 1 (PTBP1) is involved in specific protein sub-complexes that control gene expression during apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL)
Summary
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. 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. B12 or related compounds may prove to be useful therapeutic agents for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s Neurodegenerative diseases such as Parkinson’s (PD) and Alzheimer’s (AD) are characterized by the progressive loss of specific neuronal cell populations, and are associated with the formation of protein aggregates[1,2,3]. We used protein expression profiling combined with pathway analysis to investigate the molecular events associated with the protective effects, and gained insight into the underlying mechanisms of oxidative damage and neuroprotection
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