Heat stress activates interleukin-8 and the antioxidant system via Nrf2 pathways in human dental pulp cells.
ABSTRACT This study tested whether heat stress (42 degrees C for 30 minutes) induces reactive oxygen species (ROS), proinflammatory cytokines, Nrf2 activation, and Nrf2 target genes such as antioxidant enzymes in human dental pulp (HDP) cells.
ROS was evaluated by using flow cytometry. Proteins and messenger RNA levels for cytokines and antioxidant genes were determined by using Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) analysis, respectively.
Heat stress induced the production of ROS and the increased expression of the interleukin (IL)-8 and IL-8 receptor genes. Exposure of cells to heat stress resulted in the nuclear translocation of Nrf2 and increased expression of Nrf2 target genes including heme oxygenase-1. Pretreatment with an exogenous antioxidant inhibited the heat-induced expression of IL-8 and Nrf2 target genes and Nrf2 translocation.
Collectively, these results show that heat-induced Nrf2 activation is the major regulatory pathway of cytoprotective gene expression against oxidative stress in HDP cells.
Article: Nitrosamines and water.[Show abstract] [Hide abstract]
ABSTRACT: This paper provides an overview of all current issues that are connected to the presence of nitrosamines in water technology. N-nitrosodimethylamine (NDMA) is the most frequently detected member of this family. Nitrosamines became the hottest topic in drinking water science when they were identified as disinfection by-products (DBPs) in chloraminated waters. The danger that they pose to consumer health seems to be much higher than that from chlorinated DBPs. This review summarizes our contemporary knowledge of these compounds in water, their occurrence, and precursors of nitrosamines in drinking and wastewaters, in addition to attempts to remove nitrosamines from water. The paper also reviews our knowledge of the mechanisms of nitrosamine formation in water technology. The current, commonly accepted mechanism of NDMA formation during chloramination of drinking waters assumes that dichloramine reacts with dimethylamine, forms unsymmetrical dimethylhydrazine and further oxidizes to NDMA. The question to answer is which precursors are responsible for delivering the DMA moiety for the reaction since the presence of DMA in water cannot explain the quantities of NDMA that are formed. There are also reports that other oxidants that are commonly used in water technology may generate NDMA. However, the mechanisms of such transformations are unknown. Methods for the removal of nitrosamines from water are described briefly. However, the research that has been undertaken on such methods seems to be at an early stage of development. It is predicted that photolytic methods may have the greatest potential for technological application.Journal of hazardous materials 02/2011; 189(1-2):1-18. · 4.14 Impact Factor
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ABSTRACT: Recognition and repair of cellular damage is crucial if organisms are to survive harmful environmental conditions. In mammals, the Keap1 protein orchestrates this response, but how it perceives adverse circumstances is not fully understood. Herein, we implicate NO, Zn(2+), and alkenals, endogenously occurring chemicals whose concentrations increase during stress, in this process. By combining molecular modeling with phylogenetic, chemical, and functional analyses, we show that Keap1 directly recognizes NO, Zn(2+), and alkenals through three distinct sensors. The C288 alkenal sensor is of ancient origin, having evolved in a common ancestor of bilaterans. The Zn(2+) sensor minimally comprises H225, C226, and C613. The most recent sensor, the NO sensor, emerged coincident with an expansion of the NOS gene family in vertebrates. It comprises a cluster of basic amino acids (H129, K131, R135, K150, and H154) that facilitate S-nitrosation of C151. Taken together, our data suggest that Keap1 is a specialized sensor that quantifies stress by monitoring the intracellular concentrations of NO, Zn(2+), and alkenals, which collectively serve as second messengers that may signify danger and/or damage.Proceedings of the National Academy of Sciences 10/2010; 107(44):18838-43. · 9.81 Impact Factor
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ABSTRACT: Introduction The objective of this study was to evaluate the biocompatibility, inflammatory response, and odontoblastic potential of Biodentine (Septodont, Saint Maur des Fosses, France), Ortho-MTA (OMTA; BioMTA, Seoul, Korea), Angelus-MTA (AMTA; Angelus, Londrina, Brazil), and IRM (Dentsply Tulsa Dental, Tulsa, OK) in human dental pulp cells. The underlying signaling mechanisms were also investigated. Methods Biocompatibilities were examined by the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide assay. Differentiation was assessed by alkaline phosphatase activity, alizarin red S staining, and reverse-transcription polymerase chain reaction for marker genes. The levels of inflammatory mediators and cytokines were measured by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Signal transduction analysis was performed by Western blotting. Results Biodentine, OMTA, and AMTA showed favorable cell proliferation, alkaline phosphatase activity, formation of mineralized nodules, and expression of odontoblastic marker genes that were similar to those of IRM. The levels of proinflammatory mediators including nitric oxide, prostaglandin E2, inducible nitric oxide synthase, and cyclooxygenase-2 were lower for Biodentine, OMTA, and AMTA compared with the IRM group. All test materials induced reactive oxygen species production and the expression of hemeoxygenase-1, nuclear factor–E2-related factor-2, and mitogen-activated protein kinases. Conclusions These data indicate for the first time that the biocompatibility, inflammatory response, and odontoblastic differentiation of Biodentine were similar to that of OMTA and AMTA in HDPCs, which suggests that Biodentine could be good alternative pulp capping agent.Journal of Endodontics. 01/2014;