Redox/methylation mediated abnormal DNA methylation as regulators of ambient fine particulate matter-induced neurodevelopment related impairment in human neuronal cells
机构：[1]Shanghai Jiao Tong University School of Public Health ,Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Shanghai 200025, China[2]Shanghai Jiao Tong University School of Environmental Science and Engineering, Shanghai, 200240, China [3]Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
Fine particulate matter (PM2.5) has been implicated as a risk factor for neurodevelopmental disorders including autism in children. However, the underlying biological mechanism remains unclear. DNA methylation is suggested to be a fundamental mechanism for the neuronal responses to environmental cues. We prepared whole particle of PM2.5 (PM2.5), water-soluble extracts (Pw), organic extracts (Po) and carbon core component (Pc) and characterized their chemical constitutes. We found that PM2.5 induced significant redox imbalance, decreased the levels of intercellular methyl donor S-adenosylmethionine and caused global DNA hypomethylation. Furthermore, PM2.5 exposure triggered gene-specific promoter DNA hypo-or hypermethylation and abnormal mRNA expression of autism candidate genes. PM2.5-induced DNA hypermethylation in promoter regions of synapse related genes were associated with the decreases in their mRNA and protein expression. The inhibiting effects of antioxidative reagents, a methylation-supporting agent and a DNA methyltransferase inhibitor demonstrated the involvement of redox/methylation mechanism in PM2.5-induced abnormal DNA methylation patterns and synaptic protein expression. The biological effects above generally followed a sequence of PM2.5 >= Pwo > Po > Pw > Pc. Our results implicated a novel epigenetic mechanism for the neurodevelopmental toxicity of particulate air pollution, and that eliminating the chemical components could mitigate the neurotoxicity of PM2.5.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81502771]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2015M570374]; Interdisciplinary Program of Shanghai Jiao Tong University [YG2015MS01]
第一作者机构：[1]Shanghai Jiao Tong University School of Public Health ,Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Shanghai 200025, China
通讯作者：
通讯机构：[1]Shanghai Jiao Tong University School of Public Health ,Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Shanghai 200025, China[3]Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
推荐引用方式(GB/T 7714)：
Wei Hongying,Liang Fan,Meng Ge,et al.Redox/methylation mediated abnormal DNA methylation as regulators of ambient fine particulate matter-induced neurodevelopment related impairment in human neuronal cells[J].SCIENTIFIC REPORTS.2016,6:doi:10.1038/srep33402.
APA：
Wei, Hongying,Liang, Fan,Meng, Ge,Nie, Zhiqing,Zhou, Ren...&Wang, Yan.(2016).Redox/methylation mediated abnormal DNA methylation as regulators of ambient fine particulate matter-induced neurodevelopment related impairment in human neuronal cells.SCIENTIFIC REPORTS,6,
MLA：
Wei, Hongying,et al."Redox/methylation mediated abnormal DNA methylation as regulators of ambient fine particulate matter-induced neurodevelopment related impairment in human neuronal cells".SCIENTIFIC REPORTS 6.(2016)
