TY - JOUR A1 - Wandt, Viktoria Klara Veronika A1 - Winkelbeiner, Nicola Lisa A1 - Bornhorst, Julia A1 - Witt, Barbara A1 - Raschke, Stefanie A1 - Simon, Luise A1 - Ebert, Franziska A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - A matter of concern BT - trace element dyshomeostasis and genomic stability in neurons JF - Redox Biology N2 - Neurons are post-mitotic cells in the brain and their integrity is of central importance to avoid neurodegeneration. Yet, the inability of self-replenishment of post-mitotic cells results in the need to withstand challenges from numerous stressors during life. Neurons are exposed to oxidative stress due to high oxygen consumption during metabolic activity in the brain. Accordingly, DNA damage can occur and accumulate, resulting in genome instability. In this context, imbalances in brain trace element homeostasis are a matter of concern, especially regarding iron, copper, manganese, zinc, and selenium. Although trace elements are essential for brain physiology, excess and deficient conditions are considered to impair neuronal maintenance. Besides increasing oxidative stress, DNA damage response and repair of oxidative DNA damage are affected by trace elements. Hence, a balanced trace element homeostasis is of particular importance to safeguard neuronal genome integrity and prevent neuronal loss. This review summarises the current state of knowledge on the impact of deficient, as well as excessive iron, copper, manganese, zinc, and selenium levels on neuronal genome stability Y1 - 2021 U6 - https://doi.org/10.1016/j.redox.2021.101877 VL - 41 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Winkelbeiner, Nicola Lisa A1 - Wandt, Viktoria Klara Veronika A1 - Ebert, Franziska A1 - Lossow, Kristina A1 - Bankoglu, Ezgi E. A1 - Martin, Maximilian A1 - Mangerich, Aswin A1 - Stopper, Helga A1 - Bornhorst, Julia A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice BT - Impact of Sex and Age JF - International Journal of Molecular Sciences N2 - Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery. KW - maintenance of genomic integrity KW - ageing KW - sex KW - DNA damage KW - base excision repair (incision activity) KW - DNA damage response KW - poly(ADP-ribosyl)ation KW - liver Y1 - 2020 U6 - https://doi.org/10.3390/ijms21186600 SN - 1422-0067 VL - 21 IS - 18 PB - Molecular Diversity Preservation International CY - Basel ER - TY - JOUR A1 - Kopp, Johannes Florian A1 - Müller, Sandra Marie A1 - Pohl, Gabriele A1 - Lossow, Kristina A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - A quick and simple method for the determination of six trace elements in mammalian serum samples using ICP-MS/MS JF - Journal of trace elements in medicine and biology N2 - In order to assess the individual trace element status of humans for either medical or scientific purposes, amongst others, blood serum levels are determined. Furthermore, animal models are used to study interactions of trace elements. Most published methods require larger amounts (500-1000 mu L) of serum to achieve a reliable determination of multiple trace elements. However, oftentimes, these amounts of serum cannot be dedicated to a single analysis and the amount available for TE-determination is much lower. Therefore, a published ICP-MS/MS method for trace element determination in serum was miniaturized, optimized and validated for the measurement of Mn, Fe, Cu Zn, I and Se in as little as 50 mu L of human and murine serum and is presented in this work. For validation, recoveries of multiple LOTs and levels from commercially available human reference serum samples were determined, infra- and inter-day variations were assessed and limits of detection and quantification determined. It is shown, that the method is capable of giving accurate and reproducible results for all six elements within the relevant concentration ranges for samples from humans living in central Europe as well as from laboratory mice. As a highlight, the achieved limits of detection and quantification for Mn were found to be at 0.02 mu g/L serum and 0.05 mu g/L serum, respectively, while using an alkaline diluent for the parallel determination of iodine. Y1 - 2019 U6 - https://doi.org/10.1016/j.jtemb.2019.04.015 SN - 0946-672X VL - 54 SP - 221 EP - 225 PB - Elsevier CY - München ER - TY - JOUR A1 - Schwarz, Maria A1 - Lossow, Kristina A1 - Kopp, Johannes Florian A1 - Schwerdtle, Tanja A1 - Kipp, Anna Patricia T1 - Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper JF - Nutrients N2 - Trace elements, like Cu, Zn, Fe, or Se, are important for the proper functioning of antioxidant enzymes. However, in excessive amounts, they can also act as pro-oxidants. Accordingly, trace elements influence redox-modulated signaling pathways, such as the Nrf2 pathway. Vice versa, Nrf2 target genes belong to the group of transport and metal binding proteins. In order to investigate whether Nrf2 directly regulates the systemic trace element status, we used mice to study the effect of a constitutive, whole-body Nrf2 knockout on the systemic status of Cu, Zn, Fe, and Se. As the loss of selenoproteins under Se-deprived conditions has been described to further enhance Nrf2 activity, we additionally analyzed the combination of Nrf2 knockout with feeding diets that provide either suboptimal, adequate, or supplemented amounts of Se. Experiments revealed that the Nrf2 knockout partially affected the trace element concentrations of Cu, Zn, Fe, or Se in the intestine, liver, and/or plasma. However, aside from Fe, the other three trace elements were only marginally modulated in an Nrf2-dependent manner. Selenium deficiency mainly resulted in increased plasma Zn levels. One putative mediator could be the metal regulatory transcription factor 1, which was up-regulated with an increasing Se supply and downregulated in Se-supplemented Nrf2 knockout mice. KW - Nrf2 KW - selenium KW - iron KW - copper KW - zinc KW - homeostasis Y1 - 2019 U6 - https://doi.org/10.3390/nu11092112 SN - 2072-6643 VL - 11 IS - 9 PB - MDPI CY - Basel ER - TY - THES A1 - Kipp, Anna Patricia T1 - Physiologische und Tumor-Assoziierte Funktionen von Selen und Selenoproteinen Y1 - 2014 ER -