The role of reactive oxygen species and hemeoxygenase-1 expression in the cytotoxicity, cell cycle alteration and apoptosis of dental pulp cells induced by BisGMA.
Biocompatibility of dentin bonding agents (DBAs) and resin composite is important to preserve the pulp vitality after operative restoration. Bisphenol-glycidyl-methacrylate (BisGMA) is one common monomer adding into DBAs and resin. In this study, we found that exposure of human dental pulp cells to BisGMA (>0.1 mM) led to cytotoxicity, G2/M cell cycle arrest and apoptosis as analyzed by propidium iodide (PI) and PI/annexin V dual fluorescent flow cytometry. These events were associated with a decline of cdc2, cdc25C and cyclinB1 expression at both mRNA and protein levels. BisGMA also induced the expression of hemeoxygenase-1 (HO-1), an oxidative stress responsive gene, in pulp cells. Catalase could prevent the BisGMA-induced alteration of cell cycle-related genes (cdc2, cdc25C, cyclinB1) and HO-1 expression in dental pulp cells. Interestingly, Zn-protoporphyrin (2.5-5 microM), a HO inhibitor, enhanced the BisGMA-induced reactive oxygen species (ROS) production and cytotoxicity. These results suggest that exposure to higher concentrations of BisGMA may stimulate ROS production, cell cycle arrest, apoptosis and cell death. Inducing the expression of HO-1 in dental pulp cells by BisGMA is mediated by ROS production and important to protect dental pulp against the toxicity by monomers present in composite resin and DBAs.
Chang
Mei-Chi
MC
Biomedical Science Team, Chang Gung Institute of Technology, Taoyuan, Taiwan.
Chen
Lin-I
LI
Chan
Chiu-Po
CP
Lee
Jang-Jaer
JJ
Wang
Tong-Mei
TM
Yang
Ting-Ting
TT
Lin
Po-Shuen
PS
Lin
Hsueh-Jen
HJ
Chang
Hsiao-Hua
HH
Jeng
Jiiang-Huei
JH
D017209:Apoptosis / Q000187:drug effects*; D017438:Bisphenol A-Glycidyl Methacrylate / Q000009:adverse effects*; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D017220:Dentin-Bonding Agents / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D011166:Porphyrins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017220:Dentin-Bonding Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; D017438:Bisphenol A-Glycidyl Methacrylate; D002374:Catalase; D051547:Heme Oxygenase-1