@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{WinkelbeinerWandtEbertetal.2020, author = {Winkelbeiner, Nicola Lisa and Wandt, Viktoria Klara Veronika and Ebert, Franziska and Lossow, Kristina and Bankoglu, Ezgi E. and Martin, Maximilian and Mangerich, Aswin and Stopper, Helga and Bornhorst, Julia and Kipp, Anna Patricia and Schwerdtle, Tanja}, title = {A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {18}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms21186600}, pages = {19}, year = {2020}, abstract = {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.}, language = {en} } @misc{WinkelbeinerWandtEbertetal.2020, author = {Winkelbeiner, Nicola Lisa and Wandt, Viktoria Klara Veronika and Ebert, Franziska and Lossow, Kristina and Bankoglu, Ezgi E. and Martin, Maximilian and Mangerich, Aswin and Stopper, Helga and Bornhorst, Julia and Kipp, Anna Patricia and Schwerdtle, Tanja}, title = {A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1021}, issn = {1866-8372}, doi = {10.25932/publishup-48483}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-484831}, pages = {21}, year = {2020}, abstract = {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.}, language = {en} } @article{ChenDeWittBornhorstetal.2015, author = {Chen, Pan and DeWitt, Margaret R. and Bornhorst, Julia and Soares, Felix A. and Mukhopadhyay, Somshuvra and Bowman, Aaron B. and Aschner, Michael A.}, title = {Age- and manganese-dependent modulation of dopaminergic phenotypes in a}, series = {Metallomics : integrated biometal science}, volume = {7}, journal = {Metallomics : integrated biometal science}, number = {2}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c4mt00292j}, pages = {289 -- 298}, year = {2015}, language = {en} } @article{MuellerEbertBornhorstetal.2018, author = {M{\"u}ller, Sandra Marie and Ebert, Franziska and Bornhorst, Julia and Galla, Hans-Joachim and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Arsenic-containing hydrocarbons disrupt a model in vitro blood-cerebrospinal fluid barrier}, series = {Journal of trace elements in medicine and biology}, volume = {49}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier GMBH}, address = {M{\"u}nchen}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2018.01.020}, pages = {171 -- 177}, year = {2018}, abstract = {Lipid-soluble arsenicals, so-called arsenolipids, have gained a lot of attention in the last few years because of their presence in many seafoods and reports showing substantial cytotoxicity emanating from arsenic-containing hydrocarbons (AsHCs), a prominent subgroup of the arsenolipids. More recent in vivo and in vitro studies indicate that some arsenolipids might have adverse effects on brain health. In the present study, we focused on the effects of selected arsenolipids and three representative metabolites on the blood-cerebrospinal fluid barrier (B-CSF-B), a brain-regulating interface. For this purpose, we incubated an in vitro model of the B-CSF-B composed of porcine choroid plexus epithelial cells (PCPECs) with three AsHCs, two arsenic-containing fatty acids (AsFAs) and three representative arsenolipid metabolites (dimethylarsinic acid, thio/oxo-dimethylpropanoic acid) to examine their cytotoxic potential and impact on barrier integrity. The toxic arsenic species arsenite was also tested in this way and served as a reference substance. While AsFAs and the metabolites showed no cytotoxic effects in the conducted assays, AsHCs showed a strong cytotoxicity, being up to 1.5-fold more cytotoxic than arsenite. Analysis of the in vitro B-CSF-B integrity showed a concentration dependent disruption of the barrier within 72 h. The correlation with the decreased plasma membrane surface area (measured as capacitance) indicates cytotoxic effects. These findings suggest exposure to elevated levels of certain arsenolipids may have detrimental consequences for the central nervous system.}, language = {en} } @article{WittBornhorstMitzeetal.2017, author = {Witt, B. and Bornhorst, Julia and Mitze, H. and Ebert, Franziska and Meyer, S. and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Arsenolipids exert less toxicity in a human neuron astrocyte co-culture as compared to the respective monocultures}, series = {Metallomics : integrated biometal science}, volume = {9}, journal = {Metallomics : integrated biometal science}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c7mt00036g}, pages = {442 -- 446}, year = {2017}, abstract = {Arsenic-containing hydrocarbons (AsHCs), natural products found in seafood, have recently been shown to exert toxic effects in human neurons. In this study we assessed the toxicity of three AsHCs in cultured human astrocytes. Due to the high cellular accessibility and substantial toxicity observed astrocytes were identified as further potential brain target cells for arsenolipids. Thereby, the AsHCs exerted a 5-19-fold higher cytotoxicity in astrocytes as compared to arsenite. Next we compared the toxicity of the arsenicals in a co-culture model of the respective human astrocytes and neurons. Notably the AsHCs did not show any substantial toxic effects in the co-culture, while arsenite did. The arsenic accessibility studies indicated that in the co-culture astrocytes protect neurons against cellular arsenic accumulation especially after incubation with arsenolipids. In summary, these data underline the importance of the glial-neuron interaction when assessing the in vitro neurotoxicity of new unclassified metal species.}, language = {en} } @article{HenzeHomannRohnetal.2016, author = {Henze, Andrea and Homann, Thomas and Rohn, Isabelle and Aschner, Michael A. and Link, Christopher D. and Kleuser, Burkhard and Schweigert, Florian J. and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin}, series = {Scientific reports}, volume = {6}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/srep37346}, pages = {12}, year = {2016}, abstract = {The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time-and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.}, language = {en} } @misc{HenzeHomannRohnetal.2016, author = {Henze, Andrea and Homann, Thomas and Rohn, Isabelle and Aschner, Michael A. and Link, Christopher D. and Kleuser, Burkhard and Schweigert, Florian J. and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-103674}, pages = {12}, year = {2016}, abstract = {The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.}, language = {en} } @article{HenzeHomannRohnetal.2016, author = {Henze, Andrea and Homann, Thomas and Rohn, Isabelle and Aschner, Michael A. and Link, Christopher D. and Kleuser, Burkhard and Schweigert, Florian J. and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin}, series = {Scientific reports}, volume = {6}, journal = {Scientific reports}, publisher = {Nature Publishing Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/srep37346}, pages = {12}, year = {2016}, abstract = {The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.}, language = {en} } @article{NicolaiBaeslerAschneretal.2020, author = {Nicolai, Merle Marie and Baesler, Jessica and Aschner, Michael and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Consequences of manganese overload in C. elegans}, series = {Naunyn-Schmiedeberg's archives of pharmacology / ed. for the Deutsche Gesellschaft f{\"u}r Experimentelle und Klinische Pharmakologie und Toxikologie}, volume = {393}, journal = {Naunyn-Schmiedeberg's archives of pharmacology / ed. for the Deutsche Gesellschaft f{\"u}r Experimentelle und Klinische Pharmakologie und Toxikologie}, number = {SUPPL 1}, publisher = {Springer}, address = {New York}, issn = {0028-1298}, doi = {10.1007/s00210-020-01828-y}, pages = {9 -- 9}, year = {2020}, language = {en} }