RRC ID 44350
Author Orimoto A, Suzuki T, Ueno A, Kawai T, Nakamura H, Kanamori T.
Title Effect of 2-hydroxyethyl methacrylate on antioxidant responsive element-mediated transcription: a possible indication of its cytotoxicity.
Journal PLoS One
Abstract BACKGROUND:The resin monomer 2-hydroxyethyl methacrylate (HEMA) is known to be more cytotoxic than methyl methacrylate (MMA). Using a luciferase reporter assay system, we previously showed that MMA activates the glutathione S-transferase alpha 1 gene (Gsta1) promoter through the anti-oxidant responsive element (ARE). However, it is not known whether HEMA induces ARE-mediated transcription.
METHODOLOGY/PRINCIPAL FINDINGS:We further developed the reporter system and studied the concentration-dependent effect of HEMA on ARE enhancer activity. The revised system employed HepG2 cells stably transfected with a destabilized luciferase reporter vector carrying 2 copies of the 41-bp ARE region of Gsta1. In this system, MMA increased ARE activity by 244-fold at 30 mM; HEMA augmented ARE activity at 3 mM more intensely than MMA (36-fold versus 11-fold) and was equipotent as MMA at 10 mM (56-fold activation); however, HEMA failed to increase ARE activity at 30 mM. In HepG2 cells, HEMA detectably lowered the cellular glutathione levels at 10 mM and cell viability at 30 mM, but MMA did not.
CONCLUSIONS:These results suggest that the low-concentration effect of HEMA on ARE activity reflects its cytotoxicity. Our reporter system used to examine ARE activity may be useful for evaluating cytotoxicities of resin monomers at concentrations lower than those for which cell viabilities are reduced.
Volume 8(3)
Pages e58907
Published 2013-1-1
DOI 10.1371/journal.pone.0058907
PII PONE-D-12-27108
PMID 23516576
PMC PMC3597541
MeSH Antioxidants / metabolism* Cell Survival / drug effects Clone Cells Cytotoxins / toxicity* Dose-Response Relationship, Drug Genes, Reporter / genetics Genetic Vectors / genetics Glutathione / metabolism Hep G2 Cells Humans Intracellular Signaling Peptides and Proteins / metabolism Intracellular Space / drug effects Intracellular Space / metabolism Kelch-Like ECH-Associated Protein 1 Luciferases / genetics Methacrylates / toxicity* Methylmethacrylates / toxicity NF-E2-Related Factor 2 / metabolism Response Elements / drug effects* Transcription, Genetic / drug effects*
IF 2.74
Times Cited 7
Human and Animal Cells Hep G2(RCB1648)