A Glimpse into the Genome-wide DNA Methylation Changes in 6-hydroxydopamine-induced In Vitro Model of Parkinson's Disease

被引:3
|
作者
Magalingam, Kasthuri Bai [1 ]
Somanath, Sushela Devi [2 ]
Radhakrishnan, Ammu Kutty [1 ]
机构
[1] Monash Univ, Jeffrey Cheah Sch Med & Hlth Sci, Bandar Sunway 47500, Malaysia
[2] Int Med Univ, Sch Med, Pathol Div, Kuala Lumpur 57000, Malaysia
关键词
Parkinson's disease; DNA methylation; GWAS; Neuroblastoma; GENE-EXPRESSION; NEURONS; NEUROTOXICITY; CEREBELLUM; AKT1;
D O I
10.5607/en22035
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
A cell-based model of Parkinson's disease (PD) is a well-established in vitro experimental prototype to investigate the disease mechanism and therapeutic approach for a potential anti-PD drug. The SH-SY5Y human neuroblastoma cells and 6-OHDA combo is one of the many neurotoxininduced neuronal cell models employed in numerous neuroscience-related research for discovering neuroprotective drug compounds. Emerging studies have reported a significant correlation between PD and epigenetic alterations, particularly DNA methylation. However, the DNA methylation changes of PD-related CpG sites on the 6-OHDA-induced toxicity on human neuronal cells have not yet been reported. We performed a genome-wide association study (GWAS) using Infinium Epic beadchip array surveying 850000 CpG sites in differentiated human neuroblastoma cells exposed to 6-OHDA. We identified 236 differentially methylated probes (DMPs) or 163 differentially methylated regions (DMRs) in 6-OHDA treated differentiated neuroblastoma cells than the untreated reference group with p<0.01, & UDelta;beta cut-off of 0.1. Among 236 DMPs, hypermethylated DMPs are 110 (47%), whereas 126 (53%) are hypomethylated. Our bioinformatic analysis revealed 3 DMRs that are significantly hypermethylated and associated with neurological disorders, namely AKT1, ITPR1 and GNG7. This preliminary study demonstrates the methylation status of PD-related CpGs in the 6-OHDA-induced toxicity in the differentiated neuroblastoma cells model.
引用
收藏
页码:119 / 132
页数:14
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