Dataset Information

Downregulation of catalase by CuO nanoparticles via hypermethylation of CpG island II on the catalase promoter.

ABSTRACT: The advent of nanotechnology has led to new applications of copper as antibiotic treatment alternatives, nanocomposite coatings, catalysts, and lubricants among others. However, few studies address the impact of nano-size copper on the molecular mechanism of eukaryotic cells. Therefore, in the present study, the human hepatic cell line (WRL-68) was used to evaluate the molecular mechanism involved in the adverse effect of CuO NPs. CuO NPs were characterized by scanning electron microscopy and dynamic light scattering to confirm their 100 nm size and their purity was determined by Fourier transform infra-red spectroscopy. The side scattered intensity in WRL-68 cells at a CuO NP concentration of 250, 500, 750 and 1000 ?M was found to be 108.83%, 126.86%, 189.03% and 250.88% respectively. The reactive oxygen species (ROS) generation at a CuO NP concentration of 1000 ?M in WRL-68 cells was 417.75%. Moreover, the ROS induced methylation of CpG island II on the catalase promoter and downregulated catalase expression at the transcriptional level in WRL-68 cells. Furthermore, the activity of the catalase enzyme was found to decrease with an increase in concentration of CuO NPs. Subsequently, the proliferation of the WRL-68 cells was increased on exposure to the CuO NPs as demonstrated by the mitochondrial activity in the MTT assay. Conclusively, it is demonstrated that exposure of CuO NPs at 1000 ?M for 24 h in the WRL-68 cell induced methylation of CpG island II via ROS on the catalase promoter and downregulated catalase expression at the transcriptional level. The obtained molecular mechanistic insights described adverse effects related to the CuO NPs.

SUBMITTER: Chibber S

PROVIDER: S-EPMC6062067 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Downregulation of catalase by CuO nanoparticles <i>via</i> hypermethylation of CpG island II on the catalase promoter.

Chibber Sandesh S Sangeet Amee A Ansari Shakeel Ahmed SA

Toxicology research 20170209 3

The advent of nanotechnology has led to new applications of copper as antibiotic treatment alternatives, nanocomposite coatings, catalysts, and lubricants among others. However, few studies address the impact of nano-size copper on the molecular mechanism of eukaryotic cells. Therefore, in the present study, the human hepatic cell line (WRL-68) was used to evaluate the molecular mechanism involved in the adverse effect of CuO NPs. CuO NPs were characterized by scanning electron microscopy and dy ...[more]

PMID: 30090500

Similar Datasets

Project description:BackgroundCpG methylation of tumor suppressor genes occurs in the early stage of carcinogenesis. Detecting risk factors for aberrant CpG methylation is clinically important for predicting cancer development. DNA methyltransferase (DNMT) 3a is considered to play critical roles in the DNA methylation process during pathogenesis. In this study, we evaluated the association between DNMT3A polymorphisms (rs6733868 and rs13428812) and CpG methylation status in non-cancerous gastric mucosa.MethodsWe determined the DNMT3A genotype and CpG methylation status of 4 genes (p14ARF, p16INK4a, DAPK, and CDH1) in 510 subjects without gastric cancer. Helicobacter pylori (HP) infection status was determined by the rapid urease test, urea breath test, speculum examination, or serum antibody test. We determined the DNMT3A genotype using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). CpG methylation status was determined by methylation-specific polymerase chain reaction (MSP). When the methylated band was stronger than 10 ng/μL according to the DNA marker, we judged CpG island hypermethylation (CIHM) to be present. Associations between genotypes and susceptibilities were assessed by logistic regression analysis.ResultsThe minor allele frequencies of both polymorphisms (rs6733868 and rs13428812) were lower in the CpG methylated groups of each of the 4 genes (p14ARF, p16INK4a, DAPK, and CDH1). Using a dominant genetic model, rs6733868 was significantly associated with the hypermethylation of each gene, whereas rs13428812 was associated with the methylation of 3 genes (all except p14ARF). When low-CIHM was defined as 1 or 2 CpG islands methylated and high-CIHM was defined as 3 or more CpG islands methylated, carrying the minor allele of rs6733868 was associated with both decreased low- and high-CIHM, and that of rs13428812 also was associated with a decrease. Comparing low-CIHM with high-CIHM, carrying the minor alleles of rs6733868 or rs13428812 was related to decreased susceptibility to high-CIHM. In HP-infected subjects, carrying the minor alleles of rs6733868 or rs13428812 had a significantly greater association with decreased susceptibility to high-CIHM.ConclusionsOur study indicates that polymorphisms of DNMT3A are associated with the accumulation of gene methylation in gastric mucosa. Carrying the minor alleles of rs6733868 or rs13428812 inhibits aberrant gene methylations, which are typically enhanced by HP infection.

Dataset Information

Downregulation of catalase by CuO nanoparticles via hypermethylation of CpG island II on the catalase promoter.

Publications

Downregulation of catalase by CuO nanoparticles <i>via</i> hypermethylation of CpG island II on the catalase promoter.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets