Differentially DNA methylation changes induced in vitro by traffic-derived nanoparticulate matter. (15th February 2018)

• Record Type: Journal Article
• Authors: Lei, Xiaoning; Muscat, Joshua E.; Zhang, Bo; Sha, Xuyang; Xiu, Guangli
• Is Part Of: Toxicology. Volume 395(2018)
• Page Start: 54
• Page End: 62
• Publication Date: 2018-02-15
• Subjects: nPM nanoparticulate matter -- PM particulate matter -- ROS reactive oxygen species -- HUVECs human umbilical vein endothelial cells -- DMP differential methylated probes -- GO gene ontology -- DMGs differential methylated genes -- KEGG Kyoto encyclopedia of genes and genomes -- TEM transmission electron microscopy -- NIST National Institute of Standards and Technology -- DCFH-DA 2′, 7′-dichlorofluorescein diacetate -- DCFH 2, 7-dichlorofluorescin -- tailDNA the percent of DNA in the tail -- SD standard deviation -- MTT tetrazolium dye -- PBS phosphate-buffered saline -- PI propidium iodide -- CpGs cytosine-phosphate-guanines -- MF molecular function -- BP biological process -- CC cellular component -- Ca2+ calcium ion -- DMD dystrophin -- PDK1 3-phosphoinositide dependent protein kinase 1 -- RYR2 ryanodine receptor 2 -- NCX1 solute carrier family 8 member A1 -- ARVD arrhythmogenic right ventricular dysplasia -- ARVC the arrhythmogenic right ventricular cardiomyopathy -- DCM pathwaydilated cardiomyopathy -- HCM hypertrophic cardiomyopathy -- ITGA1 integrin subunit alpha 1; Traffic-derived nPM -- Oxidative stress -- Differential DNA methylation -- Calcium ion -- Cardiomyopathy; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2017.11.005
• Languages: English
• ISSNs: 0300-483X

Abstract

Graphical abstract: Highlights: Cytotoxicology, apoptosis, reactive oxygen species and DNA damage induced by traffic-derived nanoparticulate matter were assessed. The epigenetics-wide DNA methylation was investigated using a new Methylation Beadchip (Illumina 850 K). The majority of enriched Gene Ontology term are known as related to calcium ion and heart muscle. The top three Kyoto encyclopedia of genes and genomes enriched pathways are involved in three common subtypes of cardiomyopathy. Abstract: The cytotoxicity, apoptosis, reactive oxygen species (ROS) and DNA damage induced by the commercial diesel exhaust particulate matter (PM) (SRM2975) with concentrations ranging from 0.1 μg mL −1 to 20 μg mL −1 were assessed in human umbilical vein endothelial cells (HUVECs) in vitro. An epigenetics-wide investigation of DNA methylation profiles was also performed using a new methylation beadchip (Illumina 850 K) to identify the health effects of traffic-derived nanoparticulate matter (nPM) with a concentration of 20 μg mL −1 . By characterising its physical and chemical properties, we found that SRM2975 is a highly disordered graphitic structure material with a nanometer dimension and a large surface area. Low levels of traffic-derived nPM (≤10 μg mL −1 ) induced cell apoptosis and DNA damage as well as increased intracellular ROS levels (p < 0.001). The HUVECs showed a significantly decreased cell viability following their exposure to traffic-derived nPM with a concentration of 20 μg mL −1 (p < 0.001). A total of 149 significant differential methylated probes between the control and traffic-derived nPM treated-cells were identified, among which 86.6% were hypermethylated. A gene ontology (GO) enrichment analysis of differential methylated genes reported that the majority of the enriched GO terms were related to calcium ion and heart muscle, and further Kyoto encyclopaedia of genes and genomes (KEGG) pathway analysis indicated that the top three enriched pathways were involved in three common subtypes of cardiomyopathy. Overall, these results demonstrated that traffic-derived nPM could induce cytotoxic effects and demonstrate robust associations with cardiomyopathy though differential DNA methylation as well as the physiologic process of ROS, oxidative stress, inflammation, cell death and calcium ion channel.