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Abstract

Objectives.
Cellular responses including cell death are induced by in vitro exposure to the unpolymerized dental monomer 2-hydroxyethyl methacrylate (HEMA). Activation of the Nrf2/ARE signaling pathway has been suggested to mediate the cellular responses. Activation of this pathway may occur either indirectly through generation of increased oxidative stress or through direct binding to cysteine thiols due to the electrophilic properties of HEMA. The objective of this study was to elucidate the potential mechanism of Nrf2/ARE pathway activation after HEMA exposure.

Methods.
Global geneexpression was investigated after exposure of the human bronchialepithelial cell line BEAS–2B to 2 mM HEMA for 4 h. After exposure to 0.5, 1 or 2 mM HEMA for up to 24 h, western analysis was performed for selected proteins. Finally, the levels of the same proteins were determined after treatment with either the antioxidants Vitamin C, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) or BSO(L-buthioninesulfoximine), an inhibitor of GSH formation.

Results.
Several of the 25 genes with the highest increase in gene transcription are related to oxidative stress responses. Increased levels of 5 corresponding proteins (HO-1, GCLC, GCLM,NQO1 and SQSTM1) were observed. Antioxidant treatment as well as inhibition of GSH did not affect upregulation of these proteins. Thus, increased ROS or reduced GSH levels appear to be of limited importance in the observed HEMA-induced changes.

Significance.
Knowledge of the cellular responses to HEMA is important to evaluate the safetyof HEMA-containing biomaterials. The results support that HEMA activates the Nrf2-AREtranscriptional pathway directly through its electrophilic properties.


Reference
The dental monomer 2-hydroxyethyl methacrylate (HEMA) causes transcriptionally regulated adaptation partially initiated by electrophilic stress.
Becher R, Valen H, Olderbø BP, Bølling AK, Samuelsen JT
Dental materials xxx (2018) xxx-xxx
DOI: https://doi.org/10.1016/j.dental.2018.11.008