Methyl methacrylate activates the Gsta1 promoter.
Residual monomers in resin-based biomaterials cause cytotoxicity. We previously showed that methyl methacrylate (MMA) induced mRNA expression of the glutathione S-transferase alpha 1 gene (Gsta1) located downstream of the cis-acting anti-oxidant responsive element (ARE). Herein, we tested the hypothesis that MMA activated the Gsta1 promoter through the ARE. HepG2 cells were transfected with a luciferase reporter vector containing the ARE and the Gsta1 promoter (-990 to +46 bp) and cultured for 12 hrs with MMA (initial concentration, 10 mM). Analysis of the expressed luciferase activity indicated that MMA activated the promoter 2.6-fold. MMA (from 1 to 30 mM) dose-dependently increased the promoter activity, which reached a plateau between 6 and 12 hrs. In HepG2 cells transfected with a reporter vector containing 2 AREs and a TATA-like promoter, 10 mM MMA increased the reporter expression 2.8-fold. These results suggest that MMA increases Gsta1 transcription through ARE-mediated promoter activation.
Hattori
N
N
Department of Periodontology, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan. srp-psho@dpc.agu.ac.jp
Suzuki
T
T
Jinno
S
S
Okeya
H
H
Ishikawa
A
A
Kondo
C
C
Hayashi
T
T
Ito
M
M
Kanamori
T
T
Kawai
T
T
Noguchi
T
T
D024506:5' Flanking Region / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002452:Cell Count; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003764:Dental Materials / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D005982:Glutathione Transferase / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D020366:Methylmethacrylate / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects / Q000235:genetics; D016385:TATA Box / Q000235:genetics; D020080:Tandem Repeat Sequences / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection
D000975:Antioxidants; D003764:Dental Materials; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D020366:Methylmethacrylate; C018855:2-tert-butylhydroquinone; D008156:Luciferases; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha