title: Methylation of PARP-1 promoter involved in the regulation of nano-SiO2-induced decrease of PARP-1 mRNA expression.
abstract: Nano silicon dioxide (nano-SiO2) is becoming more and more widely applied in the fields of industry. The potential toxic effects of nano-SiO2 and its hazard to human health are drawing more attention. The mRNA expression of poly(ADP-ribose) polymerases-1(PARP-1), a pivotal repair gene, has been decreased by nano-SiO2 exposure. However, the effect of epigenetic modification on nano-SiO2-induced low PARP-1 expression has not been reported. In this study, HaCaT cells with or without DNA methyltransferase 1(DNMT1) knock down were incubated with nano-SiO2 and then further treated with DNMT inhibitor, 5-aza-2-deoxycytidine (DAC), which is a kind of key epigenetic modification reagents. Real-time Q-PCR and western blotting were used to examine the mRNA and protein expression of PARP-1. For promoter methylation status of PARP-1, methylation-specific PCR (MSP) and Bisulfite sequencing assay were performed. Results showed a dramatic decrease of PARP-1 expression on mRNA and protein level and a simultaneously obvious increase in the level of PARP-1 methylation in nano-SiO2-treated cells compared to the control group. Further, the expression and promoter methylation of PARP-1 in HaCaT cells were restored following DNMT1 knock down, suggesting that the effects of PARP-1 promoter hypermethylation are mediated at least in part by DNMT1. Taken together, methylation of PARP-1 promoter might be involved in the regulation of nano-SiO2-induced decrease of PARP-1 expression.
authors.affiliation: School of Public Health, Zhengzhou University, 100 Kexue Boulevard Zhengzhou, Henan 450001, PR China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Gong
authors.forename: Gonghua
authors.initials: G
authors.lastname: Tao
authors.forename: Linqing
authors.initials: L
authors.lastname: Yang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Qingcheng
authors.initials: Q
authors.lastname: Liu
authors.forename: Wenjie
authors.initials: W
authors.lastname: Li
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Zhuang
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D053758:Nanoparticles; D010957:Plasmids; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012822:Silicon Dioxide; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases