TEGDMA modulates glutathione transferase P1 activity in gingival fibroblasts.
Dental resinous materials can contain large amounts (from 30 to 50%) of triethylene-glycol-dimethacrylate (TEGDMA). This compound leaches into aqueous media and is toxic to dental pulp, as well as to gingival fibroblasts in vitro. To elucidate the mechanism of TEGDMA toxicity, we investigated the effects on glutathione (GSH) level and glutathione transferase P1 (GSTP1) activity in cultured human gingival fibroblasts. TEGDMA cytotoxic concentrations (from 0.5 to 2 mM) induced a depletion of GSH without formation of oxidized GSH (GSSG). In fibroblasts expressing the wild-type GSTP1, TEGDMA both inhibited and potentiated GSTP1 activity at high (IC50 = 1.1 mM) and low concentrations, respectively. In contrast, cells expressing the GSTP1 *A/*B variant showed a weak inhibition of GST activity only, associated with greater sensitivity to drug toxicity. Biochemical analysis of GSTP1 inhibition revealed that TEGDMA is a non-competitive antagonist with respect to GSH and substrate. Thus, TEGDMA interference with GSH and GSTP1 activity may contribute to dental-resin-induced adverse effects.
Lefeuvre
M
M
Faculté de Chirurgie Dentaire, Laboratoire de Biologie et Physiopathologie Cranio-Faciale, 1 rue Maurice Arnoux, F-92120 Montrouge, France.
Bourd
K
K
Loriot
M-A
MA
Goldberg
M
M
Beaune
P
P
Périanin
A
A
Stanislawski
L
L
D002474:Cell-Free System; D002478:Cells, Cultured; D003188:Composite Resins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D005881:Gingiva / Q000187:drug effects* / Q000201:enzymology; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000235:genetics; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011109:Polymethacrylic Acids / Q000494:pharmacology*
D003188:Composite Resins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011109:Polymethacrylic Acids; C020946:triethylene glycol dimethacrylate; D011092:Polyethylene Glycols; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D005978:Glutathione; D019803:Glutathione Disulfide