| Function of MAPK and downstream transcription factors in monomer-induced apoptosis. | |
| | |
MedLine Citation:
|
PMID: 22033125 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
The resin monomer triethylene glycol dimethacrylate (TEGDMA) disrupts vital cell functions, and the production of oxidative stress is considered a common underlying mechanism. The precise signaling pathways, however, that initiate monomer-induced effects, which disturb responses of the innate immune system, inhibit dentin mineralization processes, or induce apoptosis in target cells in vitro are still unknown. The present study provides insight into the causal relationship between TEGDMA-induced apoptosis and the activation of MAPK and transcription factors downstream using pharmacological inhibitors of the ERK1/2, p38 and JNK pathways. The endotoxin lipopolysaccharide (LPS; 0.1 μg/ml) was included as an inducer of MAPK activity in RAW264.7 mouse macrophages. Cell viability was decreased from 95% in untreated cultures to about 43% after a 24 h exposure to 3 mM TEGDMA. Inhibition of the ERK1/2 pathway by the MEK1/2 inhibitor PD98059 reduced cell viability to 84%. While apoptosis induced by TEGDMA remained unchanged, Western blot analyses revealed that the activation of ERK1/2 in the presence of TEGDMA was inhibited by PD98059. LPS-induced expression of activated transcription factors c-Jun, ATF-2, ATF-3 and phospho-Elk1 was decreased in cells co-treated with TEGDMA. This inhibition was more intense in the presence of PD98059, indicating that the MEK/ERK pathway is involved in the inhibition of the LPS-induced activation of transcription factors by TEGDMA. No clear effects of the p38 inhibitor SB203580 and the JNK inhibitor SP600125 on TEGDMA-induced apoptosis were detected. The antioxidant N-acetylcysteine (NAC) protected cells from TEGDMA-induced cell death, and inhibited the activation of ERK1/2, p38 and JNK by TEGDMA. Moreover, the TEGDMA-induced downregulation of the expression of the transcription factors c-Jun and ATF-2 was prevented as well. In conclusion, physiologically relevant concentrations of inhibitors differentially modified the expression of MAPK and transcription factors in cell cultures exposed to LPS and the monomer TEGDMA. The absence of a drastic effect of the MAPK pathway inhibitors on TEGDMA-induced apoptosis on the one hand, and the protective effect of NAC and PD98059 in particular on TEGDMA-induced MAPK activation and apoptosis on the other hand, leads to a new model for the role of MAPK in the regulation of cell homeostasis in monomer-exposed cells and tissues. |
| | |
Authors:
|
Stephanie Krifka; Karl-Anton Hiller; Carola Bolay; Christine Petzel; Gianrico Spagnuolo; Franz-Xaver Reichl; Gottfried Schmalz; Helmut Schweikl |
Related Documents
:
|
20223225 - Induction of the nrf2-driven antioxidant response by tert-butylhydroquinone prevents et... 18385095 - The protective effect of quercetin against oxidative stress in the human rpe in vitro. 9568105 - Tempicol-2 (4-hydroxy-4-(2-picolyl)-2,2,6,6-tetramethylpiperidine-1-oxyl), a stable fre... 21314835 - Effects of spermidine and p-cresol on polymorphonuclear cell apoptosis and function. 16979605 - Ige isotype switch and ige production are enhanced in il-21-deficient but not ifn-gamma... 18781965 - Targeting eosinophils in asthma. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-10-25 |
Journal Detail:
|
Title: Biomaterials Volume: - ISSN: 1878-5905 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
|
Created Date: 2011-10-28 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8100316 Medline TA: Biomaterials Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
|
Department of Operative Dentistry and Periodontology, University Hospital Regensburg, University of Regensburg, D-93042 Regensburg, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Optical ray tracing-guided laser in situ keratomileusis for moderate to high myopic astigmatism.
Next Document: Management of cardiac device-related infections: A review of protocol-driven care.