@article{MeyerRaberEbertetal.2015,
  author    = {Meyer, S. and Raber, G. and Ebert, Franziska and Leffers, L. and M{\"u}ller, Sandra Marie and Taleshi, M. S. and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites},
  series = {Toxicology research},
  volume    = {5},
  journal   = {Toxicology research},
  number    = {4},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {2045-4538},
  doi       = {10.1039/c5tx00122f},
  pages     = {1289 -- 1296},
  year      = {2015},
  abstract  = {Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids.},
  language  = {en}
}
@misc{MeyerRaberEbertetal.2015,
  author    = {Meyer, S. and Raber, G. and Ebert, Franziska and Leffers, L. and M{\"u}ller, Sandra Marie and Taleshi, M. S. and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-82008},
  year      = {2015},
  abstract  = {Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids.},
  language  = {en}
}
@article{ZhouPanZhangetal.2020,
  author    = {Zhou, Suqiong and Pan, Yuanwei and Zhang, Jianguang and Li, Yan and Neumann, Falko and Schwerdtle, Tanja and Li, Wenzhong and Haag, Rainer},
  title     = {Dendritic polyglycerol-conjugated gold nanostars with different densities of functional groups to regulate osteogenesis in human mesenchymal stem cells},
  series = {Nanoscale},
  volume    = {12},
  journal   = {Nanoscale},
  number    = {47},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {2040-3364},
  doi       = {10.1039/d0nr06570f},
  pages     = {24006 -- 24019},
  year      = {2020},
  abstract  = {Nanomaterials play an important role in mimicking the biochemical and biophysical cues of the extracellular matrix in human mesenchymal stem cells (MSCs). Increasing studies have demonstrated the crucial impact of functional groups on MSCs, while limited research is available on how the functional group's density on nanoparticles regulates MSC behavior. Herein, the effects of dendritic polyglycerol (dPG)-conjugated gold nanostars (GNSs) with different densities of functional groups on the osteogenesis of MSCs are systematically investigated. dPG@GNS nanocomposites have good biocompatibility and the uptake by MSCs is in a functional group density-dependent manner. The osteogenic differentiation of MSCs is promoted by all dPG@GNS nanocomposites, in terms of alkaline phosphatase activity, calcium deposition, and expression of osteogenic protein and genes. Interestingly, the dPGOH@GNSs exhibit a slight upregulation in the expression of osteogenic markers, while the different charged densities of sulfate and amino groups show more efficacy in the promotion of osteogenesis. Meanwhile, the sulfated nanostars dPGS20@GNSs show the highest enhancement. Furthermore, various dPG@GNS nanocomposites exerted their effects by regulating the activation of Yes-associated protein (YAP) to affect osteogenic differentiation. These results indicate that dPG@GNS nanocomposites have functional group density-dependent influence on the osteogenesis of MSCs, which may provide a new insight into regulating stem cell fate.},
  language  = {en}
}
@misc{MuellerDawczynskiWiestetal.2020,
  author    = {M{\"u}ller, Sandra and Dawczynski, Christine and Wiest, Johanna and Lorkowski, Stefan and Kipp, Anna Patricia and Schwerdtle, Tanja},
  title     = {Functional Biomarkers for the Selenium Status in a Human Nutritional Intervention Study},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {878},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-46011},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-460115},
  pages     = {16},
  year      = {2020},
  abstract  = {Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not always ensured. The extent of such provision adequacy is estimated by the optimal effect range of biomarkers, which often reflects the physiological requirement. Preceding epidemiological studies indicate that low selenium serum concentrations could be related to cardiovascular diseases. Inter alia, risk factors for cardiovascular diseases are physical inactivity, overweight, as well as disadvantageous eating habits. In order to assess whether these risk factors can be modulated, a cardio-protective diet comprising fixed menu plans combined with physical exercise was applied in the German MoKaRi (modulation of cardiovascular risk factors) intervention study. We analyzed serum samples of the MoKaRi cohort (51 participants) for total selenium, GPx activity, and selenoprotein P at different timepoints of the study (0, 10, 20, 40 weeks) to explore the suitability of these selenium-associated markers as indicators of selenium status. Overall, the time-dependent fluctuations in serum selenium concentration suggest a successful change in nutritional and lifestyle behavior. Compared to baseline, a pronounced increase in GPx activity and selenoprotein P was observed, while serum selenium decreased in participants with initially adequate serum selenium content. SELENOP concentration showed a moderate positive monotonic correlation (r = 0.467, p < 0.0001) to total Se concentration, while only a weak linear relationship was observed for GPx activity versus total Se concentration (r = 0.186, p = 0.021). Evidently, other factors apart from the available Se pool must have an impact on the GPx activity, leading to the conclusion that, without having identified these factors, GPx activity should not be used as a status marker for Se},
  language  = {en}
}
@misc{WittSchaumloeffelSchaumloeffeletal.2020,
  author    = {Witt, Barbara and Schauml{\"o}ffel, Dirk and Schauml{\"o}ffel, Dirk and Schwerdtle, Tanja},
  title     = {Subcellular Localization of Copper},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {862},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-45954},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-459544},
  pages     = {27},
  year      = {2020},
  abstract  = {As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer's disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences.},
  language  = {en}
}
@misc{MaaresKeilKozaetal.2018,
  author    = {Maares, Maria and Keil, Claudia and Koza, Jenny and Straubing, Sophia and Schwerdtle, Tanja and Haase, Hajo},
  title     = {In Vitro Studies on Zinc Binding and Buffering by Intestinal Mucins},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1079},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-46907},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-469078},
  pages     = {22},
  year      = {2018},
  abstract  = {The investigation of luminal factors influencing zinc availability and accessibility in the intestine is of great interest when analyzing parameters regulating intestinal zinc resorption. Of note, intestinal mucins were suggested to play a beneficial role in the luminal availability of zinc. Their exact zinc binding properties, however, remain unknown and the impact of these glycoproteins on human intestinal zinc resorption has not been investigated in detail. Thus, the aim of this study is to elucidate the impact of intestinal mucins on luminal uptake of zinc into enterocytes and its transfer into the blood. In the present study, in vitro zinc binding properties of mucins were analyzed using commercially available porcine mucins and secreted mucins of the goblet cell line HT-29-MTX. The molecular zinc binding capacity and average zinc binding affinity of these glycoproteins demonstrates that mucins contain multiple zinc-binding sites with biologically relevant affinity within one mucin molecule. Zinc uptake into the enterocyte cell line Caco-2 was impaired by zinc-depleted mucins. Yet this does not represent their form in the intestinal lumen in vivo under zinc adequate conditions. In fact, zinc-uptake studies into enterocytes in the presence of mucins with differing degree of zinc saturation revealed zinc buffering by these glycoproteins, indicating that mucin-bound zinc is still available for the cells. Finally, the impact of mucins on zinc resorption using three-dimensional cultures was studied comparing the zinc transfer of a Caco-2/HT-29-MTX co-culture and conventional Caco-2 monoculture. Here, the mucin secreting co-cultures yielded higher fractional zinc resorption and elevated zinc transport rates, suggesting that intestinal mucins facilitate the zinc uptake into enterocytes and act as a zinc delivery system for the intestinal epithelium.},
  language  = {en}
}
@misc{SchwarzLossowKoppetal.2019,
  author    = {Schwarz, Maria and Lossow, Kristina and Kopp, Johannes F. and Schwerdtle, Tanja and Kipp, Anna Patricia},
  title     = {Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1081},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-47287},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-472873},
  pages     = {20},
  year      = {2019},
  abstract  = {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.},
  language  = {en}
}
@misc{AlkerSchwerdtleSchomburgetal.2019,
  author    = {Alker, Wiebke and Schwerdtle, Tanja and Schomburg, Lutz and Haase, Hajo},
  title     = {A Zinpyr-1-based fluorimetric microassay for free zinc in human serum},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1086},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-47283},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-472833},
  pages     = {15},
  year      = {2019},
  abstract  = {Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual's zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body's zinc status, and its suitability as a future biomarker for an individual's zinc status.},
  language  = {en}
}
@article{TaylorGoodaleRaabetal.2017,
  author    = {Taylor, Vivien and Goodale, Britton and Raab, Andrea and Schwerdtle, Tanja and Reimer, Ken and Conklin, Sean and Karagas, Margaret R. and Francesconi, Kevin A.},
  title     = {Human exposure to organic arsenic species from seafood},
  series = {The science of the total environment : an international journal for scientific research into the environment and its relationship with man},
  volume    = {580},
  journal   = {The science of the total environment : an international journal for scientific research into the environment and its relationship with man},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0048-9697},
  doi       = {10.1016/j.scitotenv.2016.12.113},
  pages     = {266 -- 282},
  year      = {2017},
  abstract  = {Seafood, including finfish, shellfish, and seaweed, is the largest contributor to arsenic (As) exposure in many human populations. In contrast to the predominance of inorganic As in water and many terrestrial foods, As in marine-derived foods is present primarily in the form of organic compounds. To date, human exposure and toxicological assessments have focused on inorganic As, while organic As has generally been considered to be nontoxic. However, the high concentrations of organic As in seafood, as well as the often complex As speciation, can lead to complications in assessing As exposure from diet. In this report, we evaluate the presence and distribution of organic As species in seafood, and combined with consumption data, address the current capabilities and needs for determining human exposure to these compounds. The analytical approaches and shortcomings for assessing these compounds are reviewed, with a focus on the best practices for characterization and quantitation. Metabolic pathways and toxicology of two important classes of organic arsenicals, arsenolipids and arsenosugars, are examined, as well as individual variability in absorption of these compounds. Although determining health outcomes or assessing a need for regulatory policies for organic As exposure is premature, the extensive consumption of seafood globally, along with the preliminary toxicological profiles of these compounds and their confounding effect on assessing exposure to inorganic As, suggests further investigations and process-level studies on organic As are needed to fill the current gaps in knowledge.},
  language  = {en}
}
@article{EbertZiemannWandtetal.2020,
  author    = {Ebert, Franziska and Ziemann, Vanessa and Wandt, Viktoria Klara Veronika and Witt, Barbara and M{\"u}ller, Sandra Marie and Guttenberger, Nikolaus and Bankoglu, Ezgi Eyluel and Stopper, Helga and Raber, Georg and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {Cellular toxicological characterization of a thioxolated arsenic-containing hydrocarbon},
  series = {Journal of trace elements in medicine and biology},
  volume    = {61},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Elsevier},
  address   = {M{\"u}nchen},
  doi       = {10.1016/j.jtemb.2020.126563},
  year      = {2020},
  abstract  = {Arsenolipids, especially arsenic-containing hydrocarbons (AsHC), are an emerging class of seafood originating contaminants. Here we toxicologically characterize a recently identified oxo-AsHC 332 metabolite, thioxo-AsHC 348 in cultured human liver (HepG2) cells. Compared to results of previous studies of the parent compound oxo-AsHC 332, thioxo-AsHC 348 substantially affected cell viability in the same concentration range but exerted about 10-fold lower cellular bioavailability. Similar to oxo-AsHC 332, thioxo-AsHC 348 did not substantially induce oxidative stress nor DNA damage. Moreover, in contrast to oxo-AsHC 332 mitochondria seem not to be a primary subcellular toxicity target for thioxo-AsHC 348. This study indicates that thioxo-AsHC 348 is at least as toxic as its parent compound oxo-AsHC 332 but very likely acts via a different mode of toxic action, which still needs to be identified.},
  language  = {en}
}