Mechanismen der durch dentale Monomere induzierten Apoptose

• Applicant: Professor Dr. Helmut Schweikl
• Subject Area: Dentistry, Oral Surgery
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 179949339

Monomers of dental composites like 2-hydroxyethyl methacrylate (HEMA) disturb the redox homeostasis in cells of the oral cavity by causing oxidative stress due to an enhanced formation of reactive oxygen species (ROS). According to a current paradigm, this is the basis of various cellular phenomena like the inhibition of the innate immune response, mineralisation capability of pulp cells or the induction of apoptosis in vitro. We have recently shown that monomer-induced apoptosis is causally related to the availability of the non-enzymatic antioxidant glutathione. Therefore, it is the aim of the present project to characterize the antioxidative system and the regulation of the cellular redox homeostasis in HEMA-exposed cells. To this end we will analyze the specific species of ROS generated, the function of NADPH oxidases, the redox status of cysteins in proteins as well as changes in the concentrations of glutathione and NADPH, a metabolite central to the generation of cellular antioxidants. Since the redox-sensitive transcription factor Nrf2 is the master regulator of the function and correlation of these particular antioxidative systems, the effect of HEMA on Nrf2 expression will be characterized as well. The understanding of these mechanisms of the cellular redox regulation will be the basis of the development of therapeutic strategies to protect tissues of the oral cavity from possible adverse effects caused by dental composites.

• DFG Programme: Research Grants
• Participating Persons: Dr. Karl-Anton Hiller; Dr. Stephanie Krifka