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Dent Mater. 2018 Nov 26. pii: S0109-5641(18)30622-5. doi: 10.1016/j.dental.2018.11.008. [Epub ahead of print]

The dental monomer 2-hydroxyethyl methacrylate (HEMA) causes transcriptionally regulated adaptation partially initiated by electrophilic stress.

Author information

1
Nordic Institute of Dental Materials, Sognsveien 70 A, NO-0855 Oslo, Norway; Norwegian Institute of Public Health, Department of Air Pollution and Noise, Postboks 222 Skøyen, 0213 Oslo, Norway. Electronic address: rune.becher@niom.no.
2
Nordic Institute of Dental Materials, Sognsveien 70 A, NO-0855 Oslo, Norway. Electronic address: h.v.rukke@niom.no.
3
Nordic Institute of Dental Materials, Sognsveien 70 A, NO-0855 Oslo, Norway. Electronic address: b.p.olderbo@niom.no.
4
Nordic Institute of Dental Materials, Sognsveien 70 A, NO-0855 Oslo, Norway; Norwegian Institute of Public Health, Department of Air Pollution and Noise, Postboks 222 Skøyen, 0213 Oslo, Norway. Electronic address: anette.kocbach@fhi.no.
5
Nordic Institute of Dental Materials, Sognsveien 70 A, NO-0855 Oslo, Norway. Electronic address: jts@niom.no.

Abstract

OBJECTIVES:

Cellular responses including cell death are induced by in vitro exposure to the un-polymerized 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 gene expression was investigated after exposure of the human bronchial epithelial cell line BEAS-2B to 2mM HEMA for 4h. After exposure to 0.5, 1 or 2mM HEMA for up to 24h, 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 safety of HEMA-containing biomaterials. The results support that HEMA activates the Nrf2-ARE transcriptional pathway directly through its electrophilic properties.

KEYWORDS:

Electrophile; HEMA; Nrf2; Transcriptomics

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