title: Analysis of Epidermal Growth Factor Receptor Related Gene Expression Changes in a Cellular and Animal Model of Parkinson's Disease.
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 relatedGJB2(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.
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju 380-701, Korea. kis5497@kku.ac.kr.
authors.forename: In-Su
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju 380-701, Korea. sushrutak@gmail.com.
authors.forename: Sushruta
authors.initials: S
authors.lastname: Koppula
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju 380-701, Korea. ifresha@nate.com.
authors.forename: Shin-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju 380-701, Korea. choidk@kku.ac.kr.
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D059467:Transcriptome
chemical_list: D017630:Connexins; C000607043:Gjb2 protein, mouse; D000072259:Connexin 26; D066246:ErbB Receptors
keywords: 1-methyl-4-phenylpyridinium; EGFR; Parkinson’s disease; SH-SY5Y cells; microarray analysis