@misc{BornhorstKippHaaseetal.2018,
  author    = {Bornhorst, Julia and Kipp, Anna Patricia and Haase, Hajo and Meyer, Soeren and Schwerdtle, Tanja},
  title     = {The crux of inept biomarkers for risks and benefits of trace elements},
  series = {Trends in Analytical Chemistry},
  volume    = {104},
  journal   = {Trends in Analytical Chemistry},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0165-9936},
  doi       = {10.1016/j.trac.2017.11.007},
  pages     = {183 -- 190},
  year      = {2018},
  abstract  = {Nowadays, the role of trace elements (TE) is of growing interest because dyshomeostasis of selenium (Se), manganese (Mn), zinc (Zn), and copper (Cu) is supposed to be a risk factor for several diseases. Thereby, research focuses on identifying new biomarkers for the TE status to allow for a more reliable description of the individual TE and health status. This review mirrors a lack of well-defined, sensitive, and selective biomarkers and summarizes technical limitations to measure them. Thus, the capacity to assess the relationship between dietary TE intake, homeostasis, and health is restricted, which would otherwise provide the basis to define adequate intake levels of single TE in both healthy and diseased humans. Besides that, our knowledge is even more limited with respect to the real life situation of combined TE intake and putative interactions between single TE.},
  language  = {en}
}
@article{FinkeWinkelbeinerLossowetal.2020,
  author    = {Finke, Hannah and Winkelbeiner, Nicola Lisa and Lossow, Kristina and Hertel, Barbara and Wandt, Viktoria Klara Veronika and Schwarz, Maria and Pohl, Gabriele and Kopp, Johannes Florian and Ebert, Franziska and Kipp, Anna Patricia and Schwerdtle, Tanja},
  title     = {Effects of a Cumulative, Suboptimal Supply of Multiple Trace Elements in Mice},
  series = {Molecular nutrition \& food research},
  volume    = {64},
  journal   = {Molecular nutrition \& food research},
  number    = {16},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1613-4125},
  doi       = {10.1002/mnfr.202000325},
  year      = {2020},
  abstract  = {Scope: Trace element (TE) deficiencies often occur accumulated, as nutritional intake is inadequate for several TEs, concurrently. Therefore, the impact of a suboptimal supply of iron, zinc, copper, iodine, and selenium on the TE status, health parameters, epigenetics, and genomic stability in mice are studied. Methods and results: Male mice receive reduced or adequate amounts of TEs for 9 weeks. The TE status is analyzed mass-spectrometrically in serum and different tissues. Furthermore, gene and protein expression of TE biomarkers are assessed with focus on liver. Iron concentrations are most sensitive toward a reduced supply indicated by increased serum transferrin levels and altered hepatic expression of iron-related genes. Reduced TE supply results in smaller weight gain but higher spleen and heart weights. Additionally, inflammatory mediators in serum and liver are increased together with hepatic genomic instability. However, global DNA (hydroxy)methylation is unaffected by the TE modulation. Conclusion: Despite homeostatic regulation of most TEs in response to a low intake, this condition still has substantial effects on health parameters. It appears that the liver and immune system react particularly sensitive toward changes in TE intake. The reduced Fe status might be the primary driver for the observed effects.},
  language  = {en}
}
@article{FredeEbertKippetal.2017,
  author    = {Frede, Katja and Ebert, Franziska and Kipp, Anna Patricia and Schwerdtle, Tanja and Baldermann, Susanne},
  title     = {Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells},
  series = {Journal of agricultural and food chemistry : a publication of the American Chemical Society},
  volume    = {65},
  journal   = {Journal of agricultural and food chemistry : a publication of the American Chemical Society},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {0021-8561},
  doi       = {10.1021/acs.jafc.7b01929},
  pages     = {5944 -- 5952},
  year      = {2017},
  abstract  = {The degeneration of the retinal pigment epithelium caused by oxidative damage is a stage of development in age related macular degeneration (AMD). The carotenoid lutein is a major macular pigment that may reduce the incidence and progression of AMD, but the underlying mechanism is currently not fully understood. Carotenoids are known to be direct antioxidants. However, carotenoids can also activate cellular pathways resulting in indirect antioxidant effects. Here, we investigate the influence of lutein on the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes in human retinal pigment epithelial cells (ARPE-19 cells) using lutein-loaded Tween40 micelles. The micelles were identified as a suitable delivery system since they were nontoxic in APRE-19 cells up to 0.04\% Tween40 and led to a cellular lutein accumulation of 62 mu M +/- 14 mu M after 24 h. Lutein significantly enhanced Nrf2 translocation to the nucleus 1.5 +/- 0.4-fold compared to that of unloaded micelles after 4 h. Furthermore, lutein treatment for 24 h significantly increased the transcripts of NAD(P)H:quinone oxidoreductase 1 (NQO1) by 1.7 +/- 0.1-fold, glutamate-cysteine ligase regulatory subunit (GCLm) by 1.4 +/- 0.1-fold, and heme oxygenase-1 (HO-1) by 1.8 +/- 0.3-fold. Moreover, we observed a significant enhancement of NQO1 activity by 1.2 +/- 0.1-fold. Collectively, this study indicates that lutein not only serves as a direct antioxidant but also activates Nrf 2 in ARPE-19 cells.},
  language  = {en}
}
@article{HauffeRathAgyapongetal.2022,
  author    = {Hauffe, Robert and Rath, Michaela and Agyapong, Wilson and Jonas, Wenke and Vogel, Heike and Schulz, Tim Julius and Schwarz, Maria and Kipp, Anna Patricia and Bl{\"u}her, Matthias and Kleinridders, Andr{\´e}},
  title     = {Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling},
  series = {Antioxidants},
  volume    = {11},
  journal   = {Antioxidants},
  edition   = {5},
  publisher = {MDPI},
  address   = {Basel, Schweiz},
  issn      = {2076-3921},
  doi       = {10.3390/antiox11050862},
  pages     = {1 -- 16},
  year      = {2022},
  abstract  = {The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.},
  language  = {en}
}
@misc{HauffeRathAgyapongetal.2022,
  author    = {Hauffe, Robert and Rath, Michaela and Agyapong, Wilson and Jonas, Wenke and Vogel, Heike and Schulz, Tim Julius and Schwarz, Maria and Kipp, Anna Patricia and Bl{\"u}her, Matthias and Kleinridders, Andr{\´e}},
  title     = {Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  publisher = {Universit{\"a}tsverlag Potsdam},
  address   = {Potsdam},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-56170},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-561709},
  pages     = {1 -- 16},
  year      = {2022},
  abstract  = {The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.},
  language  = {en}
}
@phdthesis{Kipp2014,
  author    = {Kipp, Anna Patricia},
  title     = {Physiologische und Tumor-Assoziierte Funktionen von Selen und Selenoproteinen},
  pages     = {IV, 198},
  year      = {2014},
  language  = {de}
}
@phdthesis{Kipp2008,
  author    = {Kipp, Anna Patricia},
  title     = {Selen, Selenoproteine und der Wnt-Signalweg : Regulation der gastrointestinalen Glutathionperoxidase durch β-Catenin und Beeinflussung des Wnt-Signalwegs durch den Selenstatus},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-30484},
  school      = {Universit{\"a}t Potsdam},
  year      = {2008},
  abstract  = {Das seit 1957 als essentiell klassifizierte Spurenelement Selen vermittelt seine Funktion haupts{\"a}chlich durch seinen Einbau in Selenoproteine in Form der 21. proteinogenen Aminos{\"a}ure Selenocystein. Insgesamt wurden 25 humane Gene f{\"u}r Selenoproteine identifiziert, deren genaue Funktion h{\"a}ufig noch nicht bekannt ist. Selen ist das einzige Mitglied aus der Gruppe der Mikron{\"a}hrstoffe, f{\"u}r das nach wie vor eine antikanzerogene Funktion vor allem in Bezug auf Darmkrebs postuliert wird. Die Grundlage daf{\"u}r liefert eine Interventionsstudie, bei der 1.312 Probanden f{\"u}r 4,5 Jahre mit 200 μg Selen/Tag supplementiert wurden. Dies resultierte in einer Senkung der Gesamtkrebsmortalit{\"a}t um 50 \%. Die Fragen einer optimalen Selenzufuhr, die nicht nur den Bedarf deckt, sondern auch die Entfaltung der antikanzerogenen Wirkung von Selen gew{\"a}hrleistet und die zugrunde liegenden molekularen Mechanismen sind noch ungekl{\"a}rt. Zudem liegt die Selenzufuhr bei einem Großteil der europ{\"a}ischen Bev{\"o}lkerung unter den Empfehlungen. Deshalb wurden in der vorliegenden Arbeit vier Wochen alte M{\"a}use f{\"u}r sechs Wochen marginal defizient (0,086 mg/kg Futter) bzw. selenad{\"a}quat (0,15 mg/kg Futter) gef{\"u}ttert. Dieser geringe Unterschied im Selengehalt resultierte in einer Senkung des Plasmaselenspiegels der selenarmen Tiere auf 13 \% und der GPx-Aktivit{\"a}t in der Leber auf 35 \%. Zun{\"a}chst wurde der Einfluss von Selen auf die globale Genexpression im murinen Colon mittels Microarray untersucht. Von den im Colon exprimierten Selenoproteinen reagierte die mRNA von SelW, SelH, GPx1 und SelM im Selenmangel besonders deutlich mit Expressionsverlust. Da diese Selenoproteine nicht nur im Colon, sondern auch in Leukozyten reguliert waren, sind sie auch als humane Biomarker f{\"u}r die in dieser Studie gew{\"a}hlte Schwankung des Selengehalts geeignet. Des Weiteren wurde auf Basis der Microarraydaten eine Signalweganalyse durchgef{\"u}hrt, die der Identifizierung krebsrelevanter Signalwege diente, um m{\"o}gliche molekularbiologische Erkl{\"a}rungsans{\"a}tze f{\"u}r die Rolle von Selen im Krebsgeschehen zu finden. Es zeigte sich, dass die mRNA von Schl{\"u}sselgenen des Wnt-Signalwegs wie β-Catenin, Gsk3β, Dvl2, Tle2, Lef1 und c-Myc auf Schwankungen des Selengehalts reagiert. Vor allem die Induktion von c-Myc, einem Zielgen des Wnt-Signalwegs, deutet darauf hin, dass dieser im Selenmangel tats{\"a}chlich aktiver ist als bei selenad{\"a}quater Versorgung. Ein weiterer m{\"o}glicher Erkl{\"a}rungsansatz f{\"u}r die postulierte pr{\"a}ventive Funktion von Selen gegen{\"u}ber Darmkrebs ist die gastrointestinale Glutathionperoxidase (GPx2), die physiologisch in den proliferierenden Zellen des Kryptengrunds exprimiert wird. Die Regulation dieses Enzyms durch den Wnt-Signalweg, der ebenfalls in proliferierenden Zellen aktiv ist, konnte mittels Reportergenanalyse und endogen auf mRNA- und Proteinebene in Zellkultur gezeigt werden. Die Aktivierung verk{\"u}rzter Promotorkonstrukte und die Mutation eines potentiellen Bindeelements identifizierten den f{\"u}r die Bindung von TCF und β-Catenin verantwortlichen Bereich. Als Zielgen des Wnt-Signalwegs scheint GPx2 zu den an Proliferationsprozessen beteiligten Genen zu geh{\"o}ren, was unter physiologischen Bedingungen die Aufrechterhaltung des intestinalen Epithels gew{\"a}hrleistet. Bei der Entstehung intestinaler Tumore, die in der Initiationsphase zu {\"u}ber 90 \% mit einer konstitutiven Aktivierung des Wnt-Signalwegs einhergeht, wirkt GPx2 m{\"o}glicherweise prokanzerogen. Die genaue Funktion von GPx2 w{\"a}hrend der Kanzerogenese bleibt weiter zu untersuchen.},
  language  = {de}
}
@article{KoppMuellerPohletal.2019,
  author    = {Kopp, Johannes Florian and M{\"u}ller, Sandra Marie and Pohl, Gabriele and Lossow, Kristina and Kipp, Anna Patricia and Schwerdtle, Tanja},
  title     = {A quick and simple method for the determination of six trace elements in mammalian serum samples using ICP-MS/MS},
  series = {Journal of trace elements in medicine and biology},
  volume    = {54},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Elsevier},
  address   = {M{\"u}nchen},
  issn      = {0946-672X},
  doi       = {10.1016/j.jtemb.2019.04.015},
  pages     = {221 -- 225},
  year      = {2019},
  abstract  = {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.},
  language  = {en}
}
@article{LossowSchwerdtleKipp2019,
  author    = {Lossow, Kristina and Schwerdtle, Tanja and Kipp, Anna Patricia},
  title     = {Selen und Jod: essenzielle Spurenelemente f{\"u}r die Schilddr{\"u}se},
  series = {Ern{\"a}hrungs-Umschau : Forschung \& Praxis},
  volume    = {66},
  journal   = {Ern{\"a}hrungs-Umschau : Forschung \& Praxis},
  number    = {9},
  publisher = {Umschau-Zeitschriftenverl.},
  address   = {Frankfurt, Main},
  issn      = {0174-0008},
  doi       = {10.4455/eu.2019.032},
  pages     = {M531 -- M536},
  year      = {2019},
  abstract  = {Selen und Jod sind essenzielle Spurenelemente, die gemeinsam f{\"u}r eine optimale Funktionst{\"u}chtigkeit der Schilddr{\"u}se erforderlich sind. Der Mangel eines oder beider Elemente f{\"u}hrt zu Verschiebungen auf Ebene der Schilddr{\"u}senhormonproduktion mit weitreichenden Konsequenzen f{\"u}r Stoffwechselprozesse, neurologische Entwicklung und Erkrankungen. Auch bei Autoimmunerkrankungen der Schilddr{\"u}se spielt die Versorgung mit Jod und Selen eine wichtige Rolle. Als Biomarker f{\"u}r den Selenstatus eignet sich der Gehalt des Gesamtselens oder der des Selenoproteins P im Serum. Zur Bestimmung des Jodstatus wird in der Regel der Jodgehalt im Urin herangezogen. Um den Versorgungszustand an diesen und vier weiteren essenziellen Spurenelementen besser zu erfassen, charakterisiert die Forschungsgruppe TraceAge alters- und geschlechtsspezifische Spurenelementprofile und neue funktionelle Biomarker der einzelnen Spurenelemente. Außerdem sollen Interaktionen weiterer Spurenelemente genauer untersucht werden.},
  language  = {de}
}
@inproceedings{LossowSchwarzKoppetal.2021,
  author    = {Loßow, Kristina and Schwarz, Maria and Kopp, Johannes and Schwerdtle, Tanja and Kipp, Anna Patricia},
  title     = {Age- and sex-dependent changes of trace elements and redox parameters in mice},
  series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
  volume    = {165},
  booktitle = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research},
  number    = {Suppl. 1},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {0891-5849},
  doi       = {10.1016/j.freeradbiomed.2020.12.346},
  pages     = {34},
  year      = {2021},
  language  = {en}
}
@article{ManowskyCamargoKippetal.2016,
  author    = {Manowsky, Julia and Camargo, Rodolfo Gonzalez and Kipp, Anna Patricia and Henkel, Janin and P{\"u}schel, Gerhard Paul},
  title     = {Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes},
  series = {American journal of physiology : Endocrinology and metabolism},
  volume    = {310},
  journal   = {American journal of physiology : Endocrinology and metabolism},
  publisher = {American Chemical Society},
  address   = {Bethesda},
  issn      = {0193-1849},
  doi       = {10.1152/ajpendo.00427.2015},
  pages     = {E938 -- E946},
  year      = {2016},
  abstract  = {Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the beta-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1 beta, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1 beta was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-kappa B. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50\%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKK beta, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues.},
  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}
}
@article{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 = {Nutrients},
  volume    = {12},
  journal   = {Nutrients},
  number    = {3},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2072-6643},
  doi       = {10.3390/nu12030676},
  pages     = {14},
  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}
}
@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}
}
@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}
}
@article{SchwarzLossowKoppetal.2019,
  author    = {Schwarz, Maria and Lossow, Kristina and Kopp, Johannes Florian and Schwerdtle, Tanja and Kipp, Anna Patricia},
  title     = {Crosstalk of Nrf2 with the Trace Elements Selenium, Iron, Zinc, and Copper},
  series = {Nutrients},
  volume    = {11},
  journal   = {Nutrients},
  number    = {9},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2072-6643},
  doi       = {10.3390/nu11092112},
  pages     = {18},
  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}
}
@article{SpeckmannSchulzHilleretal.2017,
  author    = {Speckmann, Bodo and Schulz, Sarah and Hiller, Franziska and Hesse, Deike and Schumacher, Fabian and Kleuser, Burkhard and Geisel, Juergen and Obeid, Rima and Grune, Tilman and Kipp, Anna Patricia},
  title     = {Selenium increases hepatic DNA methylation and modulates one-carbon metabolism in the liver of mice},
  series = {The journal of nutritional biochemistry},
  volume    = {48},
  journal   = {The journal of nutritional biochemistry},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {0955-2863},
  doi       = {10.1016/j.jnutbio.2017.07.002},
  pages     = {112 -- 119},
  year      = {2017},
  abstract  = {The average intake of the essential trace element selenium (Se) is below the recommendation in most European countries, possibly causing sub-optimal expression of selenoproteins. It is still unclear how a suboptimal Se status may affect health. To mimic this situation, mice were fed one of three physiologically relevant amounts of Se. We focused on the liver, the organ most sensitive to changes in the Se supply indicated by hepatic glutathione peroxidase activity. In addition, liver is the main organ for synthesis of methyl groups and glutathione via one-carbon metabolism. Accordingly, the impact of Se on global DNA methylation, methylation capacity, and gene expression was assessed. We observed higher global DNA methylation indicated by LINE1 methylation, and an increase of the methylation potential as indicated by higher S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio and by elevated mRNA expression of serine hydroxymethyltransferase in both or either of the Se groups. Furthermore, increasing the Se supply resulted in higher plasma concentrations of triglycerides. Hepatic expression of glycolytic and lipogenic genes revealed consistent Se dependent up-regulation of glucokinase. The sterol regulatory element-binding transcription factor 1 (Srebf1) was also up-regulated by Se. Both effects were confirmed in primary hepatocytes. In contrast to the overall Se-dependent increase of methylation capacity, the up-regulation of Srebf1 expression was paralleled by reduced local methylation of a specific CpG site within the Srebf1 gene. Thus, we provided evidence that Se-dependent effects on lipogenesis involve epigenetic mechanisms. (C) 2017 The Authors. Published by Elsevier Inc.},
  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}
}
@inproceedings{WandtWinkelbeinerLossowetal.2021,
  author    = {Wandt, Viktoria Klara Veronika and Winkelbeiner, Nicola and Loßow, Kristina and Kopp, Johannes and Simon, Luise and Ebert, Franziska and Kipp, Anna Patricia and Schwerdtle, Tanja},
  title     = {Trace elements, ageing, and sex. Impact on genome stability},
  series = {Naunyn-Schmiedeberg's archives of pharmacology},
  volume    = {394},
  booktitle = {Naunyn-Schmiedeberg's archives of pharmacology},
  number    = {Suppl. 1},
  publisher = {Springer},
  address   = {Berlin ; Heidelberg},
  issn      = {0028-1298},
  doi       = {10.1007/s00210-021-02066-6},
  pages     = {S13 -- S13},
  year      = {2021},
  language  = {en}
}
@misc{WiesnerReinholdSchreinerBaldermannetal.2017,
  author    = {Wiesner-Reinhold, Melanie and Schreiner, Monika and Baldermann, Susanne and Schwarz, Dietmar and Hanschen, Franziska S. and Kipp, Anna Patricia and Rowan, Daryl D. and Bentley-Hewitt, Kerry L. and McKenzie, Marian J.},
  title     = {Mechanisms of Selenium Enrichment and Measurement in Brassicaceous Vegetables, and Their Application to Human Health},
  series = {Frontiers in plant science},
  volume    = {8},
  journal   = {Frontiers in plant science},
  publisher = {Frontiers Research Foundation},
  address   = {Lausanne},
  issn      = {1664-462X},
  doi       = {10.3389/fpls.2017.01365},
  pages     = {20},
  year      = {2017},
  abstract  = {Selenium (Se) is an essential micronutrient for human health. Se deficiency affects hundreds of millions of people worldwide, particularly in developing countries, and there is increasing awareness that suboptimal supply of Se can also negatively affect human health. Selenium enters the diet primarily through the ingestion of plant and animal products. Although, plants are not dependent on Se they take it up from the soil through the sulphur (S) uptake and assimilation pathways. Therefore, geographic differences in the availability of soil Se and agricultural practices have a profound influence on the Se content of many foods, and there are increasing efforts to biofortify crop plants with Se. Plants from the Brassicales are of particular interest as they accumulate and synthesize Se into forms with additional health benefits, such as methylselenocysteine (MeSeCys). The Brassicaceae are also well-known to produce the glucosinolates; S-containing compounds with demonstrated human health value. Furthermore, the recent discovery of the selenoglucosinolates in the Brassicaceae raises questions regarding their potential bioefficacy. In this review we focus on Se uptake and metabolism in the Brassicaceae in the context of human health, particularly cancer prevention and immunity. We investigate the close relationship between Se and S metabolism in this plant family, with particular emphasis on the selenoglucosinolates, and consider the methodologies available for identifying and quantifying further novel Se-containing compounds in plants. Finally, we summarize the research of multiple groups investigating biofortification of the Brassicaceae and discuss which approaches might be most successful for supplying Se deficient populations in the future.},
  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}
}