Signaling pathway analysis of MPP⁺-treated human neuroblastoma SH-SY5Y cells
2014
Choi, Dong-Kug | Kim, In-su | Do, Jin Hwan
Parkinson’s disease (PD) is a common chronic neurodegenerative disorder primarily caused by death of dopaminergic neurons in the substantia nigra pars compacta (SN). Human neuroblastoma SH-SY5Y cells have been broadly utilized in studies of mechanisms of the pathogenesis underlying MPP⁺-induced PD mimics. However, the pathways impacted in MPP⁺-treated SH-SY5Y cells have not been examined at genome-wide level. Here, we examined genome-wide response of MPP⁺-treated SH-SY5Y cells with whole genome expression array including 47,231 probes and identified 169 genes that were significantly differentially expressed in a significance analysis of micro-arrays. Gene ontology (GO) terms such as GO:0051900 (regulation of mitochondrial depolarization), GO:0008637 (apoptotic mitochondrial changes), GO:0090090 (negative regulation of canonical Wnt receptor signaling pathway), and GO:0009968 (negative regulation of signal transduction) were significantly overrepresented in a differentially expressed genes (DEGs) analysis. The DEG information and their fold changes in expression were used to identify the pathways impacted. Five pathways, including systemic lupus erythematosus, alcoholism, prion diseases, the Wnt signaling pathway, and axon guidance had a significant impact at a threshold of P G = 0.05. Our results suggest that MPP⁺ toxicity of SH-SY5Y cells might be related to transcriptional dysregulation by a nucleosome structural defect, endoplasmic reticulum stress, and inhibited canonical Wnt signaling.
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