Abstract
We employed transcriptome analysis of epidermal growth factor receptor related gene expression changes in cellular and animal models of Parkinson’s disease (PD). We used a well-known Parkinsonian toxin 1-methyl-4-phenylpyridine (MPP+) to induce neuronal apoptosis in the human neuroblastoma SH-SY5Y cell line. The MPP+-treatment of SH-SY5Y cells was capable of inducing neuro-apoptosis, but it remains unclear what kinds of transcriptional genes are affected by MPP+ toxicity. Therefore the pathways that were significantly perturbed in MPP+ treated human neuroblastoma SH-SY5Y cells were identified based on genome-wide gene expression data at two time points (24 and 48 h). We found that the Epidermal Growth Factor Receptor (EGFR) pathway-related genes showed significantly differential expression at all time points. The EGFR pathway has been linked to diverse cellular events such as proliferation, differentiation, and apoptosis. Further, to evaluate the functional significance of the altered EGFR related gene expression observed in MPP+-treated SH-SY5Y cells, the EGFR related GJB2 (Cx26) gene expression was analyzed in an MPP+-intoxicated animal PD model. Our findings identify that the EGFR signaling pathway and its related genes, such as Cx26, might play a significant role in dopaminergic (DAergic) neuronal cell death during the process of neuro-apoptosis and therefore can be focused on as potential targets for therapeutic intervention.
Highlights
Parkinson’s disease (PD) is the second most long-term degenerative disorder of the central nervous system and is associated with a progressive loss of dopaminergic (DAergic) neurons in the substantia nigra
Several toxin-induced in vitro models such as 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA), or rotenone have been widely used in studies to understand the pathogenesis of PD, and, in many aspects, the DAergic neuronal death observed in these conditions is similar to that observed in PD
SH-SY5Yneuroblastoma cells show great potential as a useful research model for research on various CNS diseases such as neurodegenerative diseases, in which DAergic neuronal injury is prominent in the pathophysiology
Summary
Parkinson’s disease (PD) is the second most long-term degenerative disorder of the central nervous system and is associated with a progressive loss of dopaminergic (DAergic) neurons in the substantia nigra. The pathogenesis of PD is not yet clear, evidence suggests that oxidative stress-induced mitochondrial dysfunction, associated with inhibition of respiratory chain complex I, is one of the main reasons for the onset of PD [1,2]. The symptoms of PD have been achieved using neurotoxin 1-methyl-4-phenylpyridinium (MPP+), which selectively and potently inhibits complex I of the mitochondrial electron transport chain [3,4,5,6]. Several toxin-induced in vitro models such as 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA), or rotenone have been widely used in studies to understand the pathogenesis of PD, and, in many aspects, the DAergic neuronal death observed in these conditions is similar to that observed in PD.
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