@article{WittStibollerRaschkeetal.2021, author = {Witt, Barbara and Stiboller, Michael and Raschke, Stefanie and Friese, Sharleen and Ebert, Franziska and Schwerdtle, Tanja}, title = {Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers}, series = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS}, volume = {65}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS}, publisher = {Elsevier}, address = {M{\"u}nchen}, issn = {1878-3252}, doi = {10.1016/j.jtemb.2021.126711}, pages = {9}, year = {2021}, abstract = {Background: Being an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer?s disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. Methods: In this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. Results: Copper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 ?M) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. Conclusion: One potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases.}, language = {en} } @article{WandtWinkelbeinerBornhorstetal.2021, author = {Wandt, Viktoria Klara Veronika and Winkelbeiner, Nicola Lisa and Bornhorst, Julia and Witt, Barbara and Raschke, Stefanie and Simon, Luise and Ebert, Franziska and Kipp, Anna Patricia and Schwerdtle, Tanja}, title = {A matter of concern}, series = {Redox Biology}, volume = {41}, journal = {Redox Biology}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.redox.2021.101877}, pages = {13}, year = {2021}, abstract = {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}, language = {en} } @article{RohnRaschkeAschneretal.2019, author = {Rohn, Isabelle and Raschke, Stefanie and Aschner, Michael and Tuck, Simon and Kuehnelt, Doris and Kipp, Anna Patricia and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Treatment of caenorhabditis elegans with small selenium species enhances antioxidant defense systems}, series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology}, volume = {63}, journal = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology}, number = {9}, publisher = {Wiley}, address = {Hoboken}, issn = {1613-4125}, doi = {10.1002/mnfr.201801304}, pages = {9}, year = {2019}, abstract = {ScopeSmall selenium (Se) species play a key role in Se metabolism and act as dietary sources of the essential trace element. However, they are redox-active and trigger pro- and antioxidant responses. As health outcomes are strongly species-dependent, species-specific characteristics of Se compounds are tested in vivo. Methods and resultsIn the model organism Caenorhabditis elegans (C. elegans), immediate and sustained effects of selenite, selenomethionine (SeMet), and Se-methylselenocysteine (MeSeCys) are studied regarding their bioavailability, incorporation into proteins, as well as modulation of the cellular redox status. While all tested Se compounds are bioavailable, only SeMet persistently accumulates and is non-specifically incorporated into proteins. However, the protection toward chemically-induced formation of reactive species is independent of the applied Se compound. Increased thioredoxin reductase (TXNRD) activity and changes in mRNA expression levels of antioxidant proteins indicate the activation of cellular defense mechanisms. However, in txnrd-1 deletion mutants, no protective effects of the Se species are observed anymore, which is also reflected by differential gene expression data. ConclusionSe species protect against chemically-induced reactive species formation. The identified immediate and sustained systemic effects of Se species give rise to speculations on possible benefits facing subsequent periods of inadequate Se intake.}, language = {en} } @phdthesis{Raschke2023, author = {Raschke, Stefanie}, title = {Characterization of selenium and copper in cell systems of the neurovascular unit}, doi = {10.25932/publishup-60366}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-603666}, school = {Universit{\"a}t Potsdam}, pages = {XIV, 184, v}, year = {2023}, abstract = {The trace elements, selenium (Se) and copper (Cu) play an important role in maintaining normal brain function. Since they have essential functions as cofactors of enzymes or structural components of proteins, an optimal supply as well as a well-defined homeostatic regulation are crucial. Disturbances in trace element homeostasis affect the health status and contribute to the incidence and severity of various diseases. The brain in particular is vulnerable to oxidative stress due to its extensive oxygen consumption and high energy turnover, among other factors. As components of a number of antioxidant enzymes, both elements are involved in redox homeostasis. However, high concentrations are also associated with the occurrence of oxidative stress, which can induce cellular damage. Especially high Cu concentrations in some brain areas are associated with the development and progression of neurodegenerative diseases such as Alzheimer's disease (AD). In contrast, reduced Se levels were measured in brains of AD patients. The opposing behavior of Cu and Se renders the study of these two trace elements as well as the interactions between them being particularly relevant and addressed in this work.}, language = {en} }