Genome-wide temporal responses of human neuroblastoma SH-SY5Y cells to MPP+ neurotoxicity

Abstract

The development of a stable and reliable dopaminergic (DAergic) neuronal injury model is particularly necessary for studying the pathogenesis of Parkinson’s disease (PD) and developing therapeutic strategies. As SH-SY5Y cells express the dopamine transporter (DAT), a protein expressed in DAergic neurons within the central nervous system, SH-SY5Y cells has been widely used in studies of mechanisms of 1-methyl-4-phenyl-pyridinium (MPP+)-induced neurotoxicity and the pathogenesis underlying MPP+-induced PD mimics. However, the genome-wide time dependent gene expression change of neuroblastoma SH-SY5Y cells by MPP+ toxicity has not been characterized. Here, we carried out a time series microarray experiment consisting of eight time points including time 0 (control) and 0.5, 1.5, 3, 6, 9, 12, and 24 h after MPP+ treatment using IIlumina human HT-12 expression v.4 bead array. The differentially expressed genes from time series microarray data were identified using the EDGE (Extraction of Differential Gene Expression) software package. In this study, 79 and 838 genes are considered significant at a 0.1% and 1% false-discovery rate level, respectively. Gene ontology (GO) analysis of these genes was carried out with the GOrilla web-server interactive software. GO terms such as the mitochondrial part (GO:0044429), the protein-DNA complex assembly (GO:0065004), and the nucleosome assembly (GO:0006334) had significant enrichment scores. Collectively, the information of time dependent gene expression might provide insight into the regulatory mechanisms induced by MPP+ toxicity in human neuroblastoma SH-SY5Y cells.