title: Global DNA hypomethylation: a potential mechanism in King pigeon nerve tissue damage induced by avermectin.
abstract: As an effective insecticidal and nematicidal agent, avermectin (AVM) has been widely used in agricultural production and stock farming areas. Subsequently, the residues of AVM or its active metabolites in animal manure pose a toxic threat to non-target organisms in the environment. As the most characteristic epigenetic phenomena, DNA methylation status is a useful biological signal for the toxicity assessment of environmental chemical toxicants. In this study, analyses of the overall level of genomic DNA methylation were performed, and the expression levels of DNA methyltransferases (DNMTs), as well as demethylase methyl-CpG-binding domain protein 2 (MBD2), in pigeon brain tissues after subchronic exposure (with a AVM concentration of 20 mg/kg, 40 mg/kg and 60 mg/kg, respectively) to AVM for 30, 60 and 90 days were investigated. Global DNA hypomethylation and down-regulation of DNMT mRNA expression occurred in a dose-time-dependent manner in pigeon brains. The expression level of MBD2, which functions as a demethylase, was significantly enhanced in a dose-dependent but not time-dependent manner. In addition, the elevated expression level of MBD2 had a more robust effect on genomic DNA hypomethylation compared to changes in DNMT expression. Taken together, these results suggested that subchronic dose exposures of AVM could affect the global DNA methylation status, and this mechanism is closely related to changes in the expression levels of DNMTs and MBD2.
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, 150030 Harbin, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Cao
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, 150030 Harbin, China; Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, No. 246 Xuefu Raod, Nangang District, Harbin 150001, PR China.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, 150030 Harbin, China.
authors.forename: Zi-wei
authors.initials: ZW
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, 150030 Harbin, China.
authors.forename: Hai-dong
authors.initials: HD
authors.lastname: Yao
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, 150030 Harbin, China.
authors.forename: Ci
authors.initials: C
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, 150030 Harbin, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, 150030 Harbin, China. Electronic address: shiwenxu@neau.edu.cn.
authors.forename: Shi-wen
authors.initials: SW
authors.lastname: Xu
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D010856:Columbidae / Q000235:genetics / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D007306:Insecticides / Q000378:metabolism* / Q000633:toxicity; D007559:Ivermectin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D008297:Male; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D004268:DNA-Binding Proteins; D007306:Insecticides; C115368:MBD2 protein; D012333:RNA, Messenger; D007559:Ivermectin; C019264:avermectin; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: Avermectin; DNA methylation; Nerve tissue damage; Pigeon