Magalingam Kasthuri Bai, Somanath Sushela Devi, Radhakrishnan Ammu Kutty
Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Bandar Sunway 47500, Malaysia.
Pathology Division, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia.
Exp Neurobiol. 2023 Jun 30;32(3):119-132. doi: 10.5607/en22035.
A cell-based model of Parkinson's disease (PD) is a well-established 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, Δbeta 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.
帕金森病（PD）的细胞模型是一种成熟的实验原型，用于研究疾病机制和潜在抗PD药物的治疗方法。SH-SY5Y人神经母细胞瘤细胞与6-羟基多巴胺（6-OHDA）联合使用是众多神经毒素诱导的神经元细胞模型之一，被用于许多神经科学相关研究中以发现神经保护药物化合物。新兴研究报道了PD与表观遗传改变，特别是DNA甲基化之间存在显著相关性。然而，尚未有关于6-OHDA诱导的人神经元细胞毒性中PD相关CpG位点的DNA甲基化变化的报道。我们使用Infinium Epic芯片阵列进行了全基因组关联研究（GWAS），检测了暴露于6-OHDA的分化人神经母细胞瘤细胞中的850000个CpG位点。我们在6-OHDA处理的分化神经母细胞瘤细胞中鉴定出236个差异甲基化探针（DMP）或163个差异甲基化区域（DMR），与未处理的参照组相比，p<0.01，Δβ截止值为0.1。在236个DMP中，110个（47%）为高甲基化DMP，而126个（53%）为低甲基化。我们的生物信息学分析揭示了3个显著高甲基化且与神经疾病相关的DMR，即AKT1、ITPR1和GNG7。这项初步研究证明了在分化神经母细胞瘤细胞模型中，6-OHDA诱导的毒性中PD相关CpG的甲基化状态。
