Mechanismen der durch dentale Monomere induzierten Apoptose

牙齿单体诱导细胞凋亡的机制

• 批准号: 179949339
• 负责人: Professor Dr. Helmut Schweikl
• 金额: --
• 依托单位: Poliklinik für Zahnerhaltung und Parodontologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/179949339?language=en
• 关键词: Mechanismen; der; durch; dentale; Monomere

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.

牙科复合材料的单体如甲基丙烯酸2-羟乙酯（HEMA）通过由于活性氧物质（ROS）的增强形成而引起氧化应激来扰乱口腔细胞中的氧化还原稳态。根据目前的范例，这是各种细胞现象的基础，如先天免疫反应的抑制、牙髓细胞的矿化能力或体外细胞凋亡的诱导。我们最近发现，单体诱导的细胞凋亡与非酶抗氧化剂谷胱甘肽的可用性有因果关系。因此，本项目的目的是表征抗氧化系统和在HEMA暴露的细胞中的细胞氧化还原稳态的调节。为此，我们将分析产生的ROS的特定种类，NADPH氧化酶的功能，蛋白质中半胱氨酸的氧化还原状态以及谷胱甘肽和NADPH（细胞抗氧化剂产生的代谢物）浓度的变化。由于氧化还原敏感性转录因子Nrf 2是这些特定抗氧化系统的功能和相关性的主要调节因子，因此也将表征HEMA对Nrf 2表达的影响。这些机制的细胞氧化还原调节的理解将是治疗策略的发展，以保护口腔组织从牙科复合材料造成的可能的不利影响的基础。

项目成果

Cell responses to cariogenic microorganisms and dental resin materials-Crosstalk at the dentin-pulp interface?

细胞对致龋微生物和牙科树脂材料的反应——牙本质-牙髓界面的串扰？

• DOI: 10.1016/j.dental.2017.02.006
• 发表时间: 2017
• 期刊: Dental materials : official publication of the Academy of Dental Materials
• 作者: Schweikl H;Buchalla W;Krifka S
• 通讯作者: Krifka S

Flavin-containing enzymes as a source of reactive oxygen species in HEMA-induced apoptosis.

含黄素酶作为 HEMA 诱导细胞凋亡中活性氧的来源

• DOI: 10.1016/j.dental.2017.01.014
• 发表时间: 2017
• 期刊: Dental materials : official publication of the Academy of Dental Materials
• 作者: Schweikl H;Gallorini M;Forstner M;Petzel C;Bolay C;Hiller KA;Cataldi A;Krifka S;Buchalla W
• 通讯作者: Buchalla W