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Activation of stress-regulated transcription factors by triethylene glycol dimethacrylate monomer

Paper ID Volume ID Publish Year Pages File Format Full-Text
8152 579 2011 9 PDF Available
Title
Activation of stress-regulated transcription factors by triethylene glycol dimethacrylate monomer
Abstract

Triethylene glycol dimethacrylate (TEGDMA) is a resin monomer available for short exposure scenarios of oral tissues due to incomplete polymerization processes of dental composite materials. The generation of reactive oxygen species (ROS) in the presence of resin monomers is discussed as a common mechanism underlying cellular reactions as diverse as disturbed responses of the innate immune system, inhibition of dentin mineralization processes, genotoxicity and a delayed cell cycle. Yet, the signaling pathway through a network of proteins that finally initiates the execution of monomer-induced specific cell responses is unknown so far. The aim of the present study was to extend the knowledge of molecular mechanisms of monomer-induced cell death as a basis for reasonable therapy strategies. Thus, the monomer-induced expression and phosphorylation of stress-related transcription factors was analyzed in various cell lines. The time-related induction of apoptosis was investigated as well. The expression of p53 increased in HeLa cell cultures treated with camptothecin (positive control) for 24h, and the formation of p53Ser15 and p53Ser46 was detected in cell nuclei by Western blotting. TEGDMA (3 mm) appeared to stimulate p53 expression only slightly, but increased p21 expression was found in cell nuclei and cytoplasm. Both camptothecin and TEGDMA increased p53 expression to some extent in the nuclear fraction in human transformed pulp-derived cells (tHPC), and similar effects were detected in RAW264.7 macrophages. No clear induction of c-Jun and phospho-c-Jun by TEGDMA was detected in HeLa cell nuclei, and the expression of ATF-2 and phospho-ATF-2 was inhibited in the presence of the monomer. ATF-3 expression was found only in the nuclear fraction of camptothecin-treated HeLa cultures. TEGDMA seemed to inhibit the formation of phospho-c-Jun and phospho-ATF-2 in tHPC, and the monomer acted negatively on the expression of c-Jun, ATF-2 and ATF-3 in RAW264.7 macrophages. These changes in the expression and activation of stress-related transcription factors were time-related to the induction of apoptosis by TEGDMA in all cell lines. The present study provides experimental evidence that TEGDMA interferes with the regulation of cellular pathways through transcription factors activated as a consequence of DNA damage like p53 or initiated downstream of MAPK (mitogen-activated protein kinases) like c-Jun, ATF-2 and ATF-3. The direct causal correlation between DNA damage, activation or inhibition of MAPKs and transcription factors, and apoptosis is under current investigation. However, the induction of apoptosis in different cell lines in the presence of monomers like TEGDMA may be subject to a higher level of complexity than currently suggested by simple linear models.

Keywords
Resin monomer; TEGDMA; Stress response; Transcription factor
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Activation of stress-regulated transcription factors by triethylene glycol dimethacrylate monomer
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 7, March 2011, Pages 1787–1795
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us